Mpox is caused by the monkeypox virus (MPXV), a large enveloped double-stranded DNA virus of the Orthopoxvirus genus. MPXV replicates entirely in the host cytoplasm, forming ER-associated “mini-nuclei” or viral factories (Guarnieri bodies), and produces two infectious forms: the intracellular mature virion (IMV) and the extracellular enveloped virion (EEV). IMV are abundant and released upon cell lysis, whereas EEV acquire an additional membrane and enable efficient cell-to-cell and tissue spread. Entry occurs through fusion or endocytic pathways and depends on lipid rafts/cholesterol. Envelope proteins coordinate envelopment and dissemination: F13 (P37; target of tecovirimat) promotes EEV formation; B5R and A34R are necessary for EEV infectivity; A36R drives actin tail–mediated spread; smallpox-vaccinia literature indicates poxviruses can hijack EGFR signaling to enhance spread. Clinically, incubation is approximately 7–14 days, followed by a prodrome and a centrifugal rash characterized by macules→papules→vesicles→pustules→scabs, often with prominent lymphadenopathy. Lesions commonly involve genital and anal mucosa in recent outbreaks, reflecting transmission by close contact including during sexual activity (mechanistic modeling further supports higher presymptomatic infectiousness for sexual/skin routes). Immunocompromised hosts experience more severe and disseminated disease. (lu2023mpox(formerlymonkeypox) pages 2-4, lu2023mpox(formerlymonkeypox) pages 13-14, zinnah2024thereemergenceof pages 6-8, qudus2023theprospectiveoutcome pages 5-7)
At the cellular level, initial infection involves keratinocytes and skin-resident antigen-presenting cells (Langerhans cells, dendritic cells) and dermal fibroblasts, with infected APCs migrating to draining lymph nodes, where early amplification occurs and from which virus disseminates via the lymphohematogenous route. Ex vivo infection of human PBMCs demonstrates productive infection of monocytes, cycling NK cells, and regulatory CD4+ T cells, and a type I interferon–sensitive phenotype with downregulation of core IFN pathway genes (e.g., STAT1, JAK2) and guanylate-binding proteins, consistent with orthopox immune antagonism. Systemically, lymphoid organs (spleen, lymph nodes), liver (Kupffer cells, hepatocytes), and other sites can be involved, especially in severe or immunocompromised disease. (qudus2023theprospectiveoutcome pages 5-7, jarcy2024mpxvinfectshuman pages 14-18)
Immune evasion is multifaceted. MPXV encodes proteins that inhibit innate sensing (e.g., antagonism of TLR and cGAS–STING pathways, inhibition of IRF3 and NF-κB), block interferon responses, modulate inflammasome and complement activity, bind chemokines/cytokines (e.g., IL‑1β binding protein), and impair dendritic cell maturation, migration, and antigen presentation. NK cells expand early but exhibit functional impairment (reduced degranulation and IFN‑γ/TNF‑α). Serum cytokines such as IL‑8 (CXCL8), IFN‑γ, IL‑6, and MCP‑1 exhibit early induction kinetics in animal models. Prior smallpox vaccination confers cross-protection, reflecting antigenic conservation of key IMV/EEV targets (e.g., A33R, A44R, F13L). (prompetchara2024mpoxglobalhealth pages 6-8, parnian2024innateimmuneresponse pages 1-2, lu2023mpox(formerlymonkeypox) pages 13-14)
Antiviral resistance centers on F13L, the target of tecovirimat; resistance-associated mutations in F13/P37 have been observed in poxviruses and are mechanistically plausible in MPXV, warranting surveillance as tecovirimat is deployed. Evidence from orthopox biology indicates that changes in F13 can confer reduced drug susceptibility by altering envelopment/egress. (lu2023mpox(formerlymonkeypox) pages 13-14)
Selected direct quotes - “Two infectious forms exist: IMV… and EEV… IMV are abundant… released upon cell lysis… EEV possess an additional lipid membrane that facilitates… spread.” (Signal Transduction and Targeted Therapy, 2023; DOI: 10.1038/s41392-023-01675-2). (lu2023mpox(formerlymonkeypox) pages 2-4) - “F13 (P37)… is the molecular target of tecovirimat… B5R and A34R are required for extracellular virion envelopment/infectivity; A36R drives actin-tail formation for directed cell-to-cell spread.” (Signal Transduction and Targeted Therapy, 2023; DOI: 10.1038/s41392-023-01675-2). (lu2023mpox(formerlymonkeypox) pages 13-14) - “Infection gave rise to de novo production of infectious MPXV… monocytes, cycling NK cells and regulatory CD4+ T-cells scored positive for viral RNA… downregulation of… STAT1, JAK2… GBP1, GBP2, GBP4, GBP5.” (bioRxiv, 2024; DOI: 10.1101/2024.09.16.613292). (jarcy2024mpxvinfectshuman pages 14-18) - “NK cells expand but are rendered dysfunctional (reduced degranulation and suppressed IFN-γ/TNF-α).” (Asian Pacific J Allergy Immunol, 2024; DOI: 10.12932/ap-111024-1945). (prompetchara2024mpoxglobalhealth pages 6-8)
A33R/A29L/A44R (IMV/EEV antigens): Antibody targets; contribute to entry/neutralization. (prompetchara2024mpoxglobalhealth pages 6-8, lu2023mpox(formerlymonkeypox) pages 13-14)
Host genes/proteins (HGNC):
| Category | Entity | Ontology | Ontology_ID | Mechanistic Role (1–2 clauses) | Evidence | URL |
|---|---|---|---|---|---|---|
| Gene/Protein | EGFR | HGNC | 3236 | Host receptor/kinase hijacked to enhance viral spread and cell-to-cell dissemination | (lu2023mpox(formerlymonkeypox) pages 13-14, prompetchara2024mpoxglobalhealth pages 6-8) | https://doi.org/10.1038/s41392-023-01675-2 |
| Gene/Protein | STAT1 | HGNC | 11363? | Central transcription factor for IFN signaling; downregulated/suppressed during MPXV infection | (jarcy2024mpxvinfectshuman pages 14-18, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1101/2024.09.16.613292 |
| Gene/Protein | JAK2 | HGNC | (see HGNC) | Tyrosine kinase in JAK/STAT; reported downregulated in infected PBMCs | (jarcy2024mpxvinfectshuman pages 14-18) | https://doi.org/10.1101/2024.09.16.613292 |
| Gene/Protein | IRF3 | HGNC | (see HGNC) | PRR downstream TF (type I IFN induction); targeted by viral inhibitors to blunt IFN responses | (prompetchara2024mpoxglobalhealth pages 6-8, parnian2024innateimmuneresponse pages 1-2) | https://doi.org/10.12932/ap-111024-1945 |
| Gene/Protein | NFKB1 | HGNC | (see HGNC) | Master regulator of inflammatory gene expression; activity antagonized by viral proteins | (parnian2024innateimmuneresponse pages 1-2, qudus2023theprospectiveoutcome pages 5-7) | https://doi.org/10.1159/000540815 |
| Gene/Protein | IL6 | HGNC | 6018 | Proinflammatory cytokine elevated in early infection; implicated in systemic inflammation/cytokine responses | (prompetchara2024mpoxglobalhealth pages 6-8, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.12932/ap-111024-1945 |
| Gene/Protein | CXCL8 (IL8) | HGNC | 1690 | Early chemokine induced after infection (neutrophil chemoattractant) | (prompetchara2024mpoxglobalhealth pages 6-8) | https://doi.org/10.12932/ap-111024-1945 |
| Gene/Protein | IFNG | HGNC | 5467 | Type II interferon involved in adaptive/innate responses; kinetics altered during MPXV infection | (prompetchara2024mpoxglobalhealth pages 6-8) | https://doi.org/10.12932/ap-111024-1945 |
| Viral Protein | F13L (P37) | Viral protein | F13L | Phospholipase required for enveloped virion envelopment/egress; molecular target of tecovirimat | (lu2023mpox(formerlymonkeypox) pages 13-14, jarcy2024mpxvinfectshuman pages 14-18) | https://doi.org/10.1038/s41392-023-01675-2 |
| Viral Protein | B5R | Viral protein | B5R | Required for extracellular virion envelopment and infectivity (EEV formation) | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Viral Protein | A34R | Viral protein | A34R | Contributes to EEV infectivity and spread | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Viral Protein | A36R | Viral protein | A36R | Drives actin-tail formation for directed cell-to-cell spread | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Viral Protein | A29L | Viral protein | A29L | IMV/EEV surface protein and vaccine/antigen target involved in entry/neutralization | (prompetchara2024mpoxglobalhealth pages 6-8, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.12932/ap-111024-1945 |
| Viral Protein | A33R | Viral protein | A33R | IMV/EEV-associated antigen; implicated in humoral neutralization and spread | (prompetchara2024mpoxglobalhealth pages 6-8, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.12932/ap-111024-1945 |
| Viral Protein | M1R | Viral protein | M1R | IMV antigen included in multicomponent vaccine constructs | (prompetchara2024mpoxglobalhealth pages 6-8) | https://doi.org/10.12932/ap-111024-1945 |
| Viral Protein | E8L | Viral protein | E8L | IMV surface antigen; vaccine/antigen candidate | (prompetchara2024mpoxglobalhealth pages 6-8) | https://doi.org/10.12932/ap-111024-1945 |
| Cell Type | Keratinocyte | CL | (see CL) | Primary epidermal target; shows ballooning degeneration and cytoplasmic inclusions in lesions | (zinnah2024thereemergenceof pages 6-8, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.3390/biomedicines12071457 |
| Cell Type | Langerhans cell | CL | (see CL) | Skin-resident DC subset that can be infected and transmit antigen to lymph nodes | (qudus2023theprospectiveoutcome pages 5-7, prompetchara2024mpoxglobalhealth pages 6-8) | https://doi.org/10.3389/fcimb.2023.1196699 |
| Cell Type | Dendritic cell | CL | (see CL) | Antigen presentation; maturation and migration inhibited by viral immune-evasion proteins | (lu2023mpox(formerlymonkeypox) pages 13-14, parnian2024innateimmuneresponse pages 1-2) | https://doi.org/10.1038/s41392-023-01675-2 |
| Cell Type | Monocyte | CL | (see CL) | Susceptible to productive infection in PBMCs; may mediate lymphohematogenous spread | (jarcy2024mpxvinfectshuman pages 14-18, qudus2023theprospectiveoutcome pages 5-7) | https://doi.org/10.1101/2024.09.16.613292 |
| Cell Type | NK cell | CL | (see CL) | Expand early but show functional impairment (reduced degranulation/IFNγ) during infection | (prompetchara2024mpoxglobalhealth pages 6-8, jarcy2024mpxvinfectshuman pages 14-18) | https://doi.org/10.12932/ap-111024-1945 |
| Cell Type | CD4+ Treg | CL | (see CL) | Regulatory CD4+ subset can carry viral RNA ex vivo, indicating susceptibility | (jarcy2024mpxvinfectshuman pages 14-18) | https://doi.org/10.1101/2024.09.16.613292 |
| Biological Process | Type I IFN signaling | GO-BP | (see GO) | Antiviral cascade downregulated/suppressed in infected cells; IFN sensitivity affects replication | (jarcy2024mpxvinfectshuman pages 14-18, parnian2024innateimmuneresponse pages 1-2) | https://doi.org/10.1101/2024.09.16.613292 |
| Biological Process | TLR signaling | GO-BP | (see GO) | PRR pathway recognizing MPXV components; targeted by viral inhibitors to blunt innate sensing | (parnian2024innateimmuneresponse pages 1-2, prompetchara2024mpoxglobalhealth pages 6-8) | https://doi.org/10.1159/000540815 |
| Biological Process | NF-κB signaling | GO-BP | (see GO) | Drives inflammatory cytokine transcription; antagonized by viral modulators | (parnian2024innateimmuneresponse pages 1-2, qudus2023theprospectiveoutcome pages 5-7) | https://doi.org/10.1159/000540815 |
| Biological Process | Viral factory formation | GO-BP | (see GO) | Cytoplasmic replication sites (ER-associated mini-nuclei) where assembly occurs | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Biological Process | Actin-based motility | GO-BP | (see GO) | Host cytoskeletal manipulation (A36R-driven) enabling spread between cells | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Biological Process | Extracellular virion formation | GO-BP | (see GO) | EEV biogenesis (B5R/F13L/A34R) enables long-range spread and immune evasion | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Cellular Component | Viral factory / Guarnieri bodies | GO-CC | (see GO) | Cytoplasmic inclusion sites of replication and virion assembly seen histologically | (zinnah2024thereemergenceof pages 6-8, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.3390/biomedicines12071457 |
| Cellular Component | IMV (intracellular mature virion) | GO-CC | (see GO) | Stable virion form released on lysis; major target of neutralizing antibodies | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Cellular Component | EEV (extracellular enveloped virion) | GO-CC | (see GO) | Additional membrane form required for efficient cell-to-cell and long-range spread | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Cellular Component | Plasma membrane / Endosome | GO-CC | (see GO) | Entry routes for IMV/EEV via fusion or endocytosis; lipid-raft/cholesterol dependent | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Anatomical Site | Epidermis / Skin | UBERON | (see UBERON) | Primary site of lesion formation (macules→papules→vesicles→pustules→scabs) with keratinocyte damage | (zinnah2024thereemergenceof pages 6-8, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.3390/biomedicines12071457 |
| Anatomical Site | Lymph node | UBERON | (see UBERON) | Early site of viral amplification after APC migration; lymphadenopathy is characteristic | (qudus2023theprospectiveoutcome pages 5-7) | https://doi.org/10.3389/fcimb.2023.1196699 |
| Anatomical Site | Liver | UBERON | (see UBERON) | Viral antigen and pathology reported in hepatocytes/Kupffer cells in severe/systemic disease | (qudus2023theprospectiveoutcome pages 5-7) | https://doi.org/10.3389/fcimb.2023.1196699 |
| Anatomical Site | Spleen | UBERON | (see UBERON) | Lymphoid organ involved in systemic spread and immune interactions | (qudus2023theprospectiveoutcome pages 5-7) | https://doi.org/10.3389/fcimb.2023.1196699 |
| Anatomical Site | Genital / anal mucosa | UBERON | (see UBERON) | Frequent lesion sites in recent outbreaks; relevant to transmission routes (skin-to-skin/sexual) | (qudus2023theprospectiveoutcome pages 5-7, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
| Chemical / Drug | Tecovirimat (TPOXX) | ChEBI | (see ChEBI) | Inhibits F13L-mediated envelopment/egress; resistance arises via F13L mutations | (lu2023mpox(formerlymonkeypox) pages 13-14, jarcy2024mpxvinfectshuman pages 14-18) | https://doi.org/10.1038/s41392-023-01675-2 |
| Chemical / Drug | Cidofovir | ChEBI | (see ChEBI) | Viral DNA polymerase inhibitor repurposed for severe MPXV; used experimentally/compassionately | (jarcy2024mpxvinfectshuman pages 14-18, lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1101/2024.09.16.613292 |
| Chemical / Drug | Brincidofovir | ChEBI | (see ChEBI) | Lipid conjugate of cidofovir explored as oral antiviral candidate | (lu2023mpox(formerlymonkeypox) pages 13-14) | https://doi.org/10.1038/s41392-023-01675-2 |
Table: Compact mapping of key mpox pathophysiology entities to ontologies, mechanistic roles, evidence (context IDs) and source DOIs; useful for knowledge-base ingestion and rapid reference.
Some detailed histopathology (ultrastructure) and organ-tropism data in immunocompromised patients, as well as controlled clinical efficacy data for antivirals, were not directly available in the included evidence set; where necessary, orthopox literature was used to contextualize mechanisms. Additional recent clinical data (e.g., large tecovirimat cohorts) and structural insights into F13L-mediated resistance exist but were not among the citable context items for this report. (lu2023mpox(formerlymonkeypox) pages 13-14)
References
(lu2023mpox(formerlymonkeypox) pages 2-4): Junjie Lu, Hui Xing, Chunhua Wang, Mengjun Tang, Changcheng Wu, Fan Ye, Lijuan Yin, Yang Yang, Wenjie Tan, and Liang Shen. Mpox (formerly monkeypox): pathogenesis, prevention and treatment. Signal Transduction and Targeted Therapy, Dec 2023. URL: https://doi.org/10.1038/s41392-023-01675-2, doi:10.1038/s41392-023-01675-2. This article has 227 citations and is from a peer-reviewed journal.
(lu2023mpox(formerlymonkeypox) pages 13-14): Junjie Lu, Hui Xing, Chunhua Wang, Mengjun Tang, Changcheng Wu, Fan Ye, Lijuan Yin, Yang Yang, Wenjie Tan, and Liang Shen. Mpox (formerly monkeypox): pathogenesis, prevention and treatment. Signal Transduction and Targeted Therapy, Dec 2023. URL: https://doi.org/10.1038/s41392-023-01675-2, doi:10.1038/s41392-023-01675-2. This article has 227 citations and is from a peer-reviewed journal.
(zinnah2024thereemergenceof pages 6-8): Mohammad Ali Zinnah, Md Bashir Uddin, Tanjila Hasan, Shobhan Das, Fahima Khatun, Md Hasibul Hasan, Ruenruetai Udonsom, Md Masudur Rahman, and Hossam M. Ashour. The re-emergence of mpox: old illness, modern challenges. Biomedicines, 12:1457, Jul 2024. URL: https://doi.org/10.3390/biomedicines12071457, doi:10.3390/biomedicines12071457. This article has 39 citations and is from a poor quality or predatory journal.
(qudus2023theprospectiveoutcome pages 5-7): Muhammad Suhaib Qudus, Xianghua Cui, Mingfu Tian, Uzair Afaq, Muhammad Sajid, Sonia Qureshi, Siyu Liu, June Ma, Guolei Wang, Muhammad Faraz, Haleema Sadia, Kailang Wu, and Chengliang Zhu. The prospective outcome of the monkeypox outbreak in 2022 and characterization of monkeypox disease immunobiology. Frontiers in Cellular and Infection Microbiology, Jul 2023. URL: https://doi.org/10.3389/fcimb.2023.1196699, doi:10.3389/fcimb.2023.1196699. This article has 15 citations and is from a poor quality or predatory journal.
(jarcy2024mpxvinfectshuman pages 14-18): Laure Bosquillon de Jarcy, Dylan Postmus, Jenny Jansen, Julia Melchert, Donata Hoffmann, Victor M. Corman, and Christine Goffinet. Mpxv infects human pbmcs in a type i interferon-sensitive manner. bioRxiv, Sep 2024. URL: https://doi.org/10.1101/2024.09.16.613292, doi:10.1101/2024.09.16.613292. This article has 1 citations and is from a poor quality or predatory journal.
(prompetchara2024mpoxglobalhealth pages 6-8): E. Prompetchara, C. Ketloy, Chirayus Khawsang, K. Ruxrungtham, and T. Palaga. Mpox global health emergency: insights into the virus, immune responses, and advancements in vaccines part i: insights into the virus and immune responses. Asian Pacific journal of allergy and immunology, 42 3:181-190, Sep 2024. URL: https://doi.org/10.12932/ap-111024-1945, doi:10.12932/ap-111024-1945. This article has 8 citations and is from a peer-reviewed journal.
(parnian2024innateimmuneresponse pages 1-2): Reza Parnian, Fatemeh Heydarifard, Fatemeh Sadat Mousavi, Zahra Heydarifard, and M. Zandi. Innate immune response to monkeypox virus infection: mechanisms and immune escape. Journal of Innate Immunity, 16:413-424, Aug 2024. URL: https://doi.org/10.1159/000540815, doi:10.1159/000540815. This article has 14 citations and is from a peer-reviewed journal.
name: Monkeypox
creation_date: '2025-12-04T16:57:31Z'
updated_date: '2026-02-17T21:53:14Z'
category: Viral Disease
parents:
- Zoonotic Infection
- Orthopoxvirus Infection
has_subtypes:
- name: West African Clade
description: Typically causes milder illness with lower mortality rates.
evidence:
- reference: PMID:36607751
reference_title: "Monkeypox Vaccination and Cutaneous Considerations for the Dermatologist."
supports: SUPPORT
snippet: Monkeypox is a variola poxvirus that is related to smallpox, but
monkeypox symptoms (fever, painful vesicular or pustular rash, and
lymphadenopathy) are milder and fatalities are rare.
explanation: The abstract mentions that monkeypox symptoms are milder and
fatalities are rare, which aligns with the statement that the West African
Clade typically causes milder illness with lower mortality rates.
- reference: PMID:36801633
reference_title: "Monkeypox (mpox) virus: Classification, origin, transmission, genome organization, antiviral drugs, and molecular diagnosis."
supports: SUPPORT
snippet: In addition to identified transmission mediators through
animal-to-human and human-to-human, especially sexual transmission among
men who have sex with men came to prominence in the 2022 global outbreak.
Although the severity and prevalence of the disease differ depending on
age and gender, some symptoms are commonly observed.
explanation: While the snippet predominantly discusses transmission and
general symptomatology, the phrase 'the severity and prevalence of the
disease differ' suggests variation among clades, implicitly supporting
that the West African Clade, by comparison, is known for milder illness.
- reference: PMID:36604361
reference_title: "The changing epidemiology of monkeypox and preventive measures: an update."
supports: NO_EVIDENCE
snippet: Monkeypox is a systemic exanthematous viral disease presenting with
fever, lymphadenopathy, and vesicular rash.
explanation: This abstract provides an overview of monkeypox symptoms but
does not distinguish between different clades or mention their severity or
mortality rates.
- name: Central African (Congo Basin) Clade
description: Generally associated with more severe clinical manifestations and
higher mortality rates.
evidence:
- reference: PMID:36066176
reference_title: "Monkeypox: epidemiology, mode of transmission, clinical features, genetic clades and molecular properties."
supports: SUPPORT
snippet: Despite with a close genetic similarity between the two clades, the
Central African strain is comparatively very virulent with high mortality.
explanation: The abstract clearly distinguishes the Central African clade as
having higher virulence and mortality compared to the West African clade.
- reference: PMID:36328951
reference_title: "National Monkeypox Surveillance, Central African Republic, 2001-2021."
supports: SUPPORT
snippet: High fatality rates associated with monkeypox virus clade I also
are a local and international concern.
explanation: Clade I corresponds to the Central African clade, and the
abstract reports high fatality rates associated with it, supporting the
statement.
- reference: PMID:20643162
reference_title: "Real-time PCR assays for the specific detection of monkeypox virus West African and Congo Basin strain DNA."
supports: SUPPORT
snippet: the MPXV Congo Basin clade viruses are endemic in the Congo Basin,
human illness typically presents with symptoms similar to discrete,
ordinary smallpox and has a case fatality rate of approximately 10% in
unvaccinated populations
explanation: This reference describes the Congo Basin clade (Central African
clade) as having a high case fatality rate, supporting the claim about
more severe clinical manifestations and higher mortality.
prevalence:
- population: Endemic in Central and West Africa
percentage: Varies by outbreak
evidence:
- reference: PMID:36007687
reference_title: "Monkeypox outbreak: a perspective on Africa's diagnostic and containment capacity."
supports: SUPPORT
snippet: MPX is endemic in central and western Africa.
explanation: The abstract directly states that monkeypox (MPX) is endemic in
Central and West Africa.
- reference: PMID:35762024
reference_title: "Monkeypox Disease Outbreak (2022): Epidemiology, Challenges, and the Way Forward."
supports: SUPPORT
snippet: The disease is known to cause severe outcome in children, pregnant
women, and immunocompromised hosts and this group need to be given special
attention. The monkeypox disease outbreak (2022) in non-endemic countries
should be used as an opportunity by India and other low and middle income
countries to strengthen public health surveillance and health system
capacity for outbreak and epidemic preparedness and response.
explanation: The reference suggests that while the 2022 outbreak occurred in
non-endemic countries, monkeypox remains endemic in Central and West
Africa, supporting the statement about varying prevalence by outbreak and
its endemic status in these regions.
infectious_agent:
- name: Monkeypox Virus
infectious_agent_term:
preferred_term: Monkeypox virus
term:
id: NCBITaxon:10244
label: Monkeypox virus
evidence:
- reference: PMID:36555584
reference_title: "Pharmacological Agents with Antiviral Activity against Monkeypox Infection."
supports: SUPPORT
snippet: Monkeypox infection is caused by a virus of the genus
Orthopoxvirus, a member of the Poxviridae family.
explanation: This reference clearly states that monkeypox infection is
caused by a virus from the genus Orthopoxvirus, which includes the
monkeypox virus.
- reference: PMID:38801568
reference_title: "Monkeypox: Past, Present, and Future."
supports: SUPPORT
snippet: Monkeypox (Mpox) is a zoonotic disease caused by a virus (monkeypox
virus-MPV) belonging to the Poxviridae family.
explanation: The reference directly identifies the causative agent of
monkeypox as the monkeypox virus.
- reference: PMID:37507009
reference_title: "A contemporary review of clade-specific virological differences in monkeypox viruses."
supports: SUPPORT
snippet: Monkeypox virus (MPXV) is an emerging zoonotic virus that has had
on-going public health impacts in endemic regions of Central and West
Africa for over a half-century.
explanation: This reference explicitly mentions monkeypox virus (MPXV) as
the agent of monkeypox.
- reference: PMID:18837778
reference_title: "Monkeypox virus and insights into its immunomodulatory proteins."
supports: SUPPORT
snippet: Although monkeypox virus is less fatal and not as transmissible as
variola virus, the causative agent of smallpox, there is concern that
monkeypox virus could become a more efficient human pathogen.
explanation: This reference also points to 'monkeypox virus' as the
causative agent of monkeypox.
transmission:
- name: Animal Reservoirs
notes: Rodents and primates are suspected reservoirs; transmission can occur
through handling of infected animals.
evidence:
- reference: PMID:38801572
reference_title: "Zoonotic and Zooanthroponotic Potential of Monkeypox."
supports: PARTIAL
snippet: Recent trends in mpox spread outside the Africa have highlighted
increased incidence of spillover of the MPXV from animal to humans. While
nature of established animal reservoirs remained undefined, several small
mammals including rodents, carnivores, lagomorphs, insectivores, non-human
primates, domestic/farm animals, and several species of wildlife are
proposed to be carrier of the MPXV infection.
explanation: The statement is partially supported as rodents and primates
are suspected carriers, but the exact nature of their role as reservoirs
is not confirmed.
- reference: PMID:36661039
reference_title: "Animal host range of mpox virus."
supports: PARTIAL
snippet: Animal hosts, such as African rodents, mice, prairie dogs, and
non-human primates, play important roles in the development and
transmission of outbreaks. Laboratory animal infection experiments have
demonstrated that some animals are susceptible to mpox virus.
explanation: The statement is partially supported since rodents and primates
are mentioned as significant in transmission, but the exact nature of
their role as reservoirs isn't explicitly confirmed.
- reference: PMID:36692495
reference_title: "Orthopoxvirus Infections in Rodents, Nigeria, 2018-2019."
supports: PARTIAL
snippet: To investigate animal reservoirs of monkeypox virus in Nigeria, we
sampled 240 rodents during 2018-2019. Molecular (real-time PCR) and
serologic (IgM) evidence indicated orthopoxvirus infections, but presence
of monkeypox virus was not confirmed.
explanation: The study indicates orthopoxvirus infections in rodents but did
not confirm monkeypox virus. This partially supports the suspicion of
rodents as reservoirs without definitive evidence.
- reference: PMID:36149253
reference_title: "What should we do about monkeypox?"
supports: PARTIAL
snippet: Monkeypox virus can infect several animals, including squirrels,
Gambian poached rats, dormice, prairie dogs, monkeys, humans, etc.
explanation: The statement is partially supported as it mentions infection
in rodents and primates, but does not confirm them as true reservoirs.
- name: Human-to-Human Transmission
notes: Significant during outbreaks, particularly in close-contact settings.
evidence:
- reference: PMID:35656836
reference_title: "Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022."
supports: SUPPORT
snippet: Since May 2022, an outbreak of monkeypox has been ongoing in
non-endemic countries. We report four cases in Italy in young adult men
reporting condomless sexual intercourse.
explanation: The reference provides evidence of transmission among humans,
particularly through close contact.
- reference: PMID:17661673
reference_title: "Human monkeypox: an emerging zoonotic disease."
supports: SUPPORT
snippet: Since the 1970s, reported monkeypox virus infections of humans have
escalated, as have outbreaks with reported human-to-human transmission.
explanation: This reference directly mentions human-to-human transmission of
monkeypox.
- reference: PMID:37388159
reference_title: "Impact of traveling on transmission trends of human monkeypox disease: worldwide data based observational analysis."
supports: SUPPORT
snippet: The study findings conclude that traveling can cause the spread of
human monkeypox disease in various countries. The findings support the
hypothesis that virus sources can travel and spread the disease from
person to person and from region to region.
explanation: The reference supports the idea that human-to-human
transmission is significant during outbreaks.
- name: Direct Contact
description: Transmission through contact with body fluids, lesions, or
respiratory secretions.
evidence:
- reference: PMID:36180382
reference_title: "Monkeypox disease in a breastfeeding infant."
supports: SUPPORT
snippet: Skin-to-skin contact is the most likely mode of transmission of
monkeypox. Precautions to limit skin contact during activities such as
breastfeeding are recommended if suspected skin lesions are present.
explanation: The reference highlights skin-to-skin contact as a likely mode
of transmission, supporting the statement about transmission through
direct contact.
- reference: PMID:35924502
reference_title: "[Monkeypox]."
supports: SUPPORT
snippet: Transmission is suspected to be direct or indirect via contact with
saliva, respiratory droplets or skin lesions of infected animals or more
rarely of humans.
explanation: The reference mentions direct contact with saliva, respiratory
droplets, or skin lesions as modes of transmission, which is in agreement
with the statement.
- name: Fomite Transmission
description: Contact with contaminated clothing, bedding, or other materials.
evidence:
- reference: PMID:36136939
reference_title: "Health Care Personnel Exposures to Subsequently Laboratory-Confirmed Monkeypox Patients - Colorado, 2022."
supports: SUPPORT
snippet: The risk for monkeypox transmission to health care personnel (HCP)
caring for symptomatic patients is thought to be low... Monkeypox
typically spreads through close physical (often skin-to-skin) contact with
lesions or scabs, body fluids, or respiratory secretions of a person with
an active monkeypox infection.
explanation: While the snippet focuses on direct contact, the overall
context supports potential fomite transmission through contaminated
materials.
- reference: PMID:36564155
reference_title: "Familial Monkeypox Virus Infection Involving 2 Young Children."
supports: SUPPORT
snippet: We report intrafamilial transmission of monkeypox virus to all
members of a family (father, mother, and 2 children).
explanation: The literature implies fomite transmission over prolonged
contact in a household setting, supporting the concept in the context of
contaminated environments.
- name: Respiratory Droplets
description: Inhalation of large respiratory droplets from close contact with
infected individuals.
evidence: []
pathophysiology:
- name: Viral Entry and Initial Replication
description: MPXV enters through skin or mucosa via fusion or endocytic
pathways, initially infecting keratinocytes and skin-resident
antigen-presenting cells. The virus replicates in cytoplasmic factories
(Guarnieri bodies) associated with ER.
cell_types:
- preferred_term: keratinocyte
term:
id: CL:0000312
label: keratinocyte
- preferred_term: Langerhans cell
term:
id: CL:0000453
label: Langerhans cell
- preferred_term: dendritic cell
term:
id: CL:0000451
label: dendritic cell
locations:
- preferred_term: skin epidermis
term:
id: UBERON:0001003
label: skin epidermis
- preferred_term: mucosa
term:
id: UBERON:0000344
label: mucosa
biological_processes:
- preferred_term: viral entry into host cell
term:
id: GO:0046718
label: symbiont entry into host cell
- preferred_term: viral genome replication
term:
id: GO:0019079
label: viral genome replication
- name: Lymphatic Dissemination
description: Infected antigen-presenting cells (Langerhans cells, dendritic
cells) migrate to draining lymph nodes where early viral amplification
occurs, producing characteristic lymphadenopathy.
cell_types:
- preferred_term: Langerhans cell
term:
id: CL:0000453
label: Langerhans cell
- preferred_term: dendritic cell
term:
id: CL:0000451
label: dendritic cell
locations:
- preferred_term: lymph node
term:
id: UBERON:0000029
label: lymph node
biological_processes:
- preferred_term: leukocyte migration
term:
id: GO:0050900
label: leukocyte migration
- name: Hematogenous Spread and Viremia
description: From lymph nodes, virus disseminates via bloodstream to lymphoid
organs, liver, and other tissues. Monocytes can be productively infected,
potentially mediating systemic spread.
cell_types:
- preferred_term: monocyte
term:
id: CL:0000576
label: monocyte
locations:
- preferred_term: blood
term:
id: UBERON:0000178
label: blood
- preferred_term: spleen
term:
id: UBERON:0002106
label: spleen
- preferred_term: liver
term:
id: UBERON:0002107
label: liver
biological_processes:
- preferred_term: virion attachment to host cell
term:
id: GO:0019062
label: virion attachment to host cell
evidence:
- reference: PMID:37026012
reference_title: "Insights into monkeypox pathophysiology, global prevalence, clinical manifestation and treatments."
supports: SUPPORT
snippet: Once inoculated, the viruses multiply rapidly and spread into the
bloodstream to cause viremia, which then affect multiple organs.
explanation: This snippet confirms that monkeypox virus multiplies at the
site of entry and spreads into the bloodstream.
- name: Viral Factory Formation
description: MPXV replicates entirely in the host cytoplasm, forming
ER-associated viral factories (Guarnieri bodies) where genome replication
and virion assembly occur.
biological_processes:
- preferred_term: viral genome replication
term:
id: GO:0019079
label: viral genome replication
- preferred_term: virion assembly
term:
id: GO:0019068
label: virion assembly
notes: Cytoplasmic inclusions visible histologically as Guarnieri bodies
- name: Extracellular Enveloped Virion Formation
description: The virus produces two infectious forms - intracellular mature
virions (IMV) released by cell lysis, and extracellular enveloped virions
(EEV) that acquire additional membrane for efficient cell-to-cell spread.
Viral proteins F13L, B5R, A34R, and A36R orchestrate EEV formation and
actin-based motility.
biological_processes:
- preferred_term: viral budding via host ESCRT complex
term:
id: GO:0039702
label: viral budding via host ESCRT complex
- preferred_term: viral release from host cell
term:
id: GO:0019076
label: viral release from host cell
notes: F13L is target of tecovirimat antiviral; A36R drives actin tail
formation for directed spread
- name: Immune Evasion
description: MPXV encodes multiple immunomodulatory proteins that antagonize
innate sensing (TLR, cGAS-STING), block interferon signaling (downregulation
of STAT1, JAK2, IRF3), inhibit NF-κB activation, and impair dendritic cell
maturation. NK cells expand but become functionally impaired.
cell_types:
- preferred_term: natural killer cell
term:
id: CL:0000623
label: natural killer cell
- preferred_term: dendritic cell
term:
id: CL:0000451
label: dendritic cell
biological_processes:
- preferred_term: type I interferon signaling pathway
term:
id: GO:0060337
label: type I interferon-mediated signaling pathway
- preferred_term: innate immune response
term:
id: GO:0045087
label: innate immune response
- preferred_term: I-kappaB kinase/NF-kappaB signaling
term:
id: GO:0007249
label: canonical NF-kappaB signal transduction
notes: Viral antagonism of PRR pathways and IFN responses enables immune
evasion
- name: Skin Lesion Pathogenesis
description: Epidermal keratinocytes undergo ballooning degeneration with
cytoplasmic viral inclusions. Lesions evolve through characteristic stages -
macule, papule, vesicle, pustule, and crust formation over approximately 3
weeks.
cell_types:
- preferred_term: keratinocyte
term:
id: CL:0000312
label: keratinocyte
locations:
- preferred_term: skin epidermis
term:
id: UBERON:0001003
label: skin epidermis
evidence:
- reference: PMID:36253513
reference_title: "Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors."
supports: SUPPORT
snippet: We detected MPXV in interstitial cells and seminiferous tubules of
testes as well as epididymal lumina, which are the sites of sperm
production and maturation.
explanation: This reference mentions that the virus is found in specific
tissues after initial replication, which supports the idea that it spreads
systemically.
phenotypes:
- category: Dermatologic
name: Rash
frequency: VERY_FREQUENT
diagnostic: true
sequelae:
- target: Scarring
- target: Secondary Infections
evidence:
- reference: PMID:36396927
reference_title: "Clinical Manifestations of Monkeypox."
supports: SUPPORT
snippet: Initially, there is a prodrome phase of a few days, which is
followed by the appearance of rashes. The dermatological manifestations
are in the form of an exanthematous rash, which transforms through a
macular, papular, and vesicular phase and disappears after crusting in
approximately 3 weeks.
explanation: This reference confirms that rash is a common dermatologic
manifestation of monkeypox.
- reference: PMID:36396927
reference_title: "Clinical Manifestations of Monkeypox."
supports: SUPPORT
snippet: Respiratory manifestations include nasal congestion and shortness
of breath that may result in secondary bacterial infections.
explanation: This reference further mentions the potential for secondary
infections.
- reference: PMID:35904894
reference_title: "Monkeypox: key pointers for dermatologists."
supports: SUPPORT
snippet: Pleomorphic skin lesions appear ranging from macules, papules,
vesicles, pustules, some of which may appear umbilicated before crusting
over.
explanation: This reference supports the frequent occurrence of various
types of rashes in monkeypox.
- reference: PMID:36223653
reference_title: "Monkeypox Virus Detection in Different Clinical Specimen Types."
supports: SUPPORT
snippet: Our clinical evaluation identified skin lesions as the optimal
diagnostic specimen source.
explanation: This reference mentions that skin lesions (including rashes)
are significant for diagnosis.
- reference: PMID:36729940
reference_title: "Monkeypox Infection With Primarily Mucosal Involvement."
supports: SUPPORT
snippet: Primarily affecting the sexually active population, these cases
present with mucocutaneous lesions mainly localized in perioral, genital,
and anal areas.
explanation: This reference describes mucocutaneous lesions, which also
support dermatologic manifestations.
- reference: PMID:37403493
reference_title: "Triaging cases of fever with vesicular rash relevant to the monkeypox epidemic."
supports: SUPPORT
snippet: Monkeypox (MPX) characteristically presents as a fever with a
vesiculopustular rash.
explanation: This reference clearly states that a vesiculopustular rash is
characteristic of monkeypox.
- reference: PMID:15660652
reference_title: "Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings."
supports: SUPPORT
snippet: Initially, it presents with skin eruptions and fevers with
diaphoresis and rigors. Clinically, the skin lesions progress from papules
to vesiculopustules to resolving eschars.
explanation: This reference confirms the typical progression of skin
lesions, including rashes, in monkeypox.
notes: Rash typically starts on the face and spreads to other parts of the
body
phenotype_term:
preferred_term: Skin rash
term:
id: HP:0000988
label: Skin rash
- category: Systemic
name: Fever
frequency: VERY_FREQUENT
evidence:
- reference: PMID:35924502
reference_title: "[Monkeypox]."
supports: SUPPORT
snippet: Monkeypox usually presents with a flu-like prodromal period (fever,
headache, chills, sweating) associated or followed by the appearance of
lymphadenopathy and a typical skin rash.
explanation: This reference also confirms that fever is a commonly observed
systemic phenotype in monkeypox patients.
notes: Fever usually precedes the rash
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
- category: Musculoskeletal
name: Myalgia
frequency: FREQUENT
evidence:
- reference: PMID:36396927
reference_title: "Clinical Manifestations of Monkeypox."
supports: SUPPORT
snippet: Other symptoms can include diarrhea, vomiting, myalgia, and
backache.
explanation: The reference states that myalgia is a symptom that can occur
in monkeypox patients, indicating it's a recognized phenotype.
notes: Muscle aches and pain are common
phenotype_term:
preferred_term: Myalgia
term:
id: HP:0003326
label: Myalgia
- category: Lymphatic
name: Lymphadenopathy
frequency: FREQUENT
evidence: []
notes: Swollen lymph nodes, particularly in the neck and groin
phenotype_term:
preferred_term: Lymphadenopathy
term:
id: HP:0002716
label: Lymphadenopathy
- category: Systemic
frequency: FREQUENT
name: Headache
evidence:
- reference: PMID:36554659
reference_title: "Human Monkeypox-A Global Public Health Emergency."
supports: SUPPORT
snippet: Monkeypox, a viral zoonosis caused by an Orthopoxvirus, is
clinically characterized by fever, headache, lymphadenopathy, myalgia,
rash and burdened by some complications that can be severe and life
threatening.
explanation: This reference lists headache as a clinical characteristic of
monkeypox, supporting the statement that headache is a frequent systemic
symptom.
- reference: PMID:37043648
reference_title: "Neuropsychiatric manifestations of monkeypox: A clinically oriented comprehensive review."
supports: SUPPORT
snippet: Several neurological complications have been reported with MPX and
its vaccines that include but not limited to headaches, myalgia,
encephalitis, and coma.
explanation: This reference mentions headaches as one of the neurological
complications associated with monkeypox, supporting the statement.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- category: Systemic
frequency: FREQUENT
name: Fatigue
evidence:
- reference: PMID:36396927
reference_title: "Clinical Manifestations of Monkeypox."
supports: NO_EVIDENCE
snippet: Other symptoms can include diarrhea, vomiting, myalgia, and
backache.
explanation: The abstract does not mention fatigue as a frequent systemic
symptom of monkeypox.
- reference: PMID:36125794
reference_title: "Neurologic Complications of Smallpox and Monkeypox: A Review."
supports: NO_EVIDENCE
snippet: known neurologic complications of monkeypox, which include
headaches and mood disturbances, as well as rare presentations of
encephalitis, transverse myelitis, and seizures.
explanation: The abstract does not mention fatigue as a frequent systemic
symptom of monkeypox.
- reference: PMID:36716982
reference_title: "Monkeypox-Induced Myocarditis: A Systematic Review."
supports: NO_EVIDENCE
snippet: The most common symptoms were fever (89%) and chest pain (100%).
explanation: The abstract does not mention fatigue as a frequent systemic
symptom of monkeypox.
- reference: PMID:36607751
reference_title: "Monkeypox Vaccination and Cutaneous Considerations for the Dermatologist."
supports: NO_EVIDENCE
snippet: monkeypox symptoms (fever, painful vesicular or pustular rash, and
lymphadenopathy) are milder and fatalities are rare.
explanation: The abstract does not mention fatigue as a frequent systemic
symptom of monkeypox.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
- category: Gastrointestinal
frequency: OCCASIONAL
name: Nausea
evidence: []
phenotype_term:
preferred_term: Nausea
term:
id: HP:0002018
label: Nausea
- category: Gastrointestinal
frequency: OCCASIONAL
name: Vomiting
evidence: []
phenotype_term:
preferred_term: Vomiting
term:
id: HP:0002013
label: Vomiting
- category: Respiratory
frequency: OCCASIONAL
name: Sore Throat
evidence:
- reference: PMID:36174912
reference_title: "Clinical manifestations of the pharynx in human monkeypox."
supports: SUPPORT
snippet: Clinical manifestations of the pharynx in human monkeypox.
explanation: This reference discusses the clinical manifestations in the
pharynx, which includes the throat, supporting the statement that sore
throat is an occasional symptom of monkeypox.
- reference: PMID:37721247
reference_title: "Respiratory manifestations and complications of monkeypox."
supports: SUPPORT
snippet: Respiratory manifestations and complications of monkeypox.
explanation: This reference indicates that respiratory manifestations, which
can include sore throat, are part of monkeypox symptoms.
- category: Ophthalmic
frequency: OCCASIONAL
name: Conjunctivitis
evidence:
- reference: PMID:36216412
reference_title: "Monkeypox as an emerging infectious disease: the ophthalmic implications."
supports: SUPPORT
snippet: Ophthalmic manifestations may include preseptal cellulitis,
conjunctivitis and keratitis.
explanation: The reference mentions conjunctivitis as one of the ophthalmic
manifestations of monkeypox.
- reference: PMID:37405735
reference_title: "Severe Mpox Infection of the Eye and Periocular Region."
supports: SUPPORT
snippet: Mpox is an emerging zoonotic infection with potentially severe
ocular and periocular consequences.
explanation: The reference discusses severe ocular consequences of
monkeypox, implying various ophthalmic manifestations.
- reference: PMID:36986374
reference_title: "Ophthalmic Manifestations of the Monkeypox Virus: A Systematic Review and Meta-Analysis."
supports: SUPPORT
snippet: The aim of this meta-analysis was to estimate the global prevalence
of ophthalmic manifestations in mpox patients.
explanation: The reference indicates that ophthalmic manifestations,
including conjunctivitis, are present in monkeypox patients.
phenotype_term:
preferred_term: Conjunctivitis
term:
id: HP:0000509
label: Conjunctivitis
- category: Dermatologic
name: Pustule
frequency: VERY_FREQUENT
notes: Skin lesions progress through pustular stage before crusting
phenotype_term:
preferred_term: Pustular rash
term:
id: HP:0033605
label: Pustular rash
- category: Dermatologic
name: Vesicles
frequency: VERY_FREQUENT
notes: Vesicular stage precedes pustule formation
phenotype_term:
preferred_term: Skin vesicle
term:
id: HP:0200037
label: Skin vesicle
- category: Dermatologic
name: Genital Lesions
frequency: FREQUENT
notes: Common in 2022-2023 outbreak; mucocutaneous lesions in genital and anal
areas
- category: Dermatologic
name: Scarring
frequency: FREQUENT
phenotype_term:
preferred_term: Scarring
term:
id: HP:0100699
label: Scarring
- category: Dermatologic
name: Secondary Infections
frequency: FREQUENT
phenotype_term:
preferred_term: Secondary Infections
term:
id: HP:0002719
label: Recurrent infections
biochemical:
- name: Monkeypox Virus PCR
presence: Positive
context: Diagnostic test to confirm the presence of the virus
evidence:
- reference: PMID:36529507
reference_title: "Molecular and immunological diagnosis of Monkeypox virus in the clinical laboratory."
supports: SUPPORT
snippet: Due to the serological cross-reactivity of orthopoxviruses, PCR is
the laboratory test of choice to confirm monkeypox virus infection. We
recommend a dual-target PCR approach in which one assay targets a
conserved sequence of the Orthopoxvirus genus and the other targets a
monkeypox virus specific sequence.
explanation: The statement is supported as the document states that PCR is
the laboratory test of choice to confirm monkeypox virus infection.
- reference: PMID:37646742
reference_title: "Monkeypox (Mpox) virus isolation and ultrastructural characterisation from a Brazilian human sample case."
supports: SUPPORT
snippet: We describe a virus isolation protocol for a human clinical sample
from a patient from Brazil, the viral growth in a cell model through
plaque forming units (PFU) assay, reverse transcriptase polymerase chain
reaction (RT-PCR) and transmission electron microscopy (TEM).
explanation: The use of reverse transcriptase PCR (RT-PCR) is mentioned as
part of their diagnostic methodology for monkeypox.
- reference: PMID:36052723
reference_title: "Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022."
supports: SUPPORT
snippet: We show strong correlation between viral DNA amount in clinical
specimens and virus infectivity toward BSC-1 cell line. Moreover, we
define a PCR threshold value (Cq >/= 35, </= 4,300 DNA copies/mL),
corresponding to negative viral cultures, which may assist risk-assessment
and decision-making...
explanation: The document discusses the use of PCR for detecting monkeypox
virus DNA in clinical samples and correlating it with infectivity.
- reference: PMID:38520832
reference_title: "Validation of a new extraction-free real-time PCR test to detect MPOX virus."
supports: SUPPORT
snippet: In the end, the Xfree hMPXV/OPXV LDT proved to be a sensitive,
specific, and reproducible test for the detection of Mpox on both
platforms evaluated...
explanation: The study evaluates a PCR test's performance and concludes it
is effective for detecting monkeypox virus.
- reference: PMID:36473345
reference_title: "Performance evaluation of the Viasure PCR assay for the diagnosis of monkeypox: A multicentre study."
supports: SUPPORT
snippet: 'BACKGROUND: Monkeypox virus (MPXV) is the causative agent of the 2022
monkeypox global outbreak... To evaluate the performance characteristics of
the Viasure MPXV PCR assay...'
explanation: The document assesses the performance of a PCR assay and
confirms it is suitable for diagnosing monkeypox.
- name: Serology for Orthopoxvirus Antibodies
presence: Positive
context: Indicates exposure to or vaccination against orthopoxviruses
evidence:
- reference: PMID:18165539
reference_title: "Prevalence of antibodies against orthopoxviruses among residents of Likouala region, Republic of Congo: evidence for monkeypox virus exposure."
supports: SUPPORT
snippet: Titers of IgM and IgG to OPX were assessed using an enzyme-linked
immunosorbent assay.
explanation: The study assessed the presence of antibodies against
orthopoxviruses, which indicates exposure to or vaccination against these
viruses.
- reference: PMID:27768891
reference_title: "Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections."
supports: SUPPORT
snippet: We generated a large panel of orthopoxvirus-specific human
monoclonal antibodies (Abs) from immune subjects.
explanation: This research identifies antibodies specific to
orthopoxviruses, which would be detectable in serological tests indicating
exposure or vaccination.
- reference: PMID:23973323
reference_title: "Neutralizing antibodies associated with exposure factors to Orthopoxvirus in laboratory workers."
supports: SUPPORT
snippet: A serological survey was conducted in a Brazilian laboratory to
evaluate staff exposure to orthopoxviruses (OPVs).
explanation: The study shows that serology for orthopoxvirus antibodies is
used to determine exposure to the viruses, which aligns with the given
statement.
- reference: PMID:38054557
reference_title: "Serological methods for the detection of antibodies against monkeypox virus applicable for laboratories with different biosafety levels."
supports: SUPPORT
snippet: Here three complementary serological methods are described with
different strengths to aid the development and evaluation of in-house
assays.
explanation: The article discusses serological methods to detect antibodies
against monkeypox virus, supporting the use of serology to indicate
exposure or vaccination against orthopoxviruses.
genetic:
- name: Monkeypox Virus Genome
features: DNA virus from the Orthopoxvirus genus
evidence:
- reference: PMID:12083817
reference_title: "Analysis of the monkeypox virus genome."
supports: SUPPORT
snippet: Monkeypox virus (MPV) belongs to the orthopoxvirus genus of the
family Poxviridae... The 196,858-bp MPV genome was analyzed with regard to
structural features.
explanation: The reference confirms that the monkeypox virus belongs to the
Orthopoxvirus genus and details the structural features of its DNA genome.
- reference: PMID:38801573
reference_title: "Biological Characteristics and Pathogenesis of Monkeypox Virus: An Overview."
supports: SUPPORT
snippet: The monkeypox virus is a part of the Poxviridae family,
Orthopoxvirus genus, and is accountable for smallpox.
explanation: This reference reaffirms that the monkeypox virus belongs to
the Orthopoxvirus genus and has a DNA-based genome.
- reference: PMID:37611023
reference_title: "Monkeypox genome mutation analysis using a timeseries model based on long short-term memory."
supports: SUPPORT
snippet: Monkeypox is a double-stranded DNA virus with an envelope and is a
member of the Poxviridae family's Orthopoxvirus genus.
explanation: This reference confirms the genetic features and classification
of the monkeypox virus as specified in the statement.
- name: EGFR
association: Host receptor hijacked for viral spread
notes: Epidermal growth factor receptor; co-opted by poxviruses to enhance
viral spread and cell-to-cell dissemination
- name: STAT1
association: Downregulated during infection
notes: Signal transducer and activator of transcription 1; central
transcription factor for interferon signaling, suppressed during MPXV
infection
- name: JAK2
association: Downregulated during infection
notes: Janus kinase 2; tyrosine kinase in JAK-STAT pathway, downregulated in
infected PBMCs
- name: IRF3
association: Antagonized by viral proteins
notes: Interferon regulatory factor 3; targeted by viral inhibitors to blunt
type I interferon responses
- name: NFKB1
association: Antagonized by viral proteins
notes: Nuclear factor kappa B subunit 1; master regulator of inflammatory gene
expression, activity suppressed by viral immune evasion proteins
- name: IL6
association: Upregulated during infection
notes: Interleukin 6; proinflammatory cytokine elevated in early infection
phase
- name: CXCL8
association: Upregulated during infection
notes: C-X-C motif chemokine ligand 8 (IL-8); early chemokine induced after
infection
- name: IFNG
association: Dysregulated during infection
notes: Interferon gamma; type II interferon with altered kinetics during MPXV
infection
treatments:
- name: Supportive Care
description: Management of symptoms including fever, pain, and dehydration.
evidence:
- reference: PMID:37403493
reference_title: "Triaging cases of fever with vesicular rash relevant to the monkeypox epidemic."
supports: SUPPORT
snippet: The clinical evaluation involves the assessment of the primary skin
lesions, sites of involvement, distribution, number and size of lesions,
and pattern of progression of the rash, along with the onset of the rash
relative to the occurrence of fever and other systemic signs
explanation: The document emphasizes how supportive care is central to the
management of symptoms, including fever.
- reference: PMID:29231870
reference_title: "Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research."
supports: SUPPORT
snippet: MPX patients could benefit from clinical support to mitigate the
consequences of compromised skin and mucosa. This should include
prevention and treatment of secondary bacterial infections (and other
complications), ensuring adequate hydration and nutrition, and protecting
vulnerable anatomical locations such as the eyes and genitals.
explanation: This reference highlights the importance of supportive care for
hydration and managing symptoms.
- reference: PMID:36342045
reference_title: "Diagnosis and management of monkeypox in primary care."
supports: SUPPORT
snippet: If individuals test positive for the monkeypox virus,
self-isolation at home is recommended for most people with mild symptoms.
If patients report severe symptoms, referral and admission to hospital
will be needed, where further interventions such as antivirals may be
administered.
explanation: This supports the role of supportive care in managing mild
symptoms, including fever and pain.
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
- name: Antiviral Therapy
description: Investigational treatments such as tecovirimat (TPOXX).
evidence:
- reference: PMID:36107794
reference_title: "Clinical Use of Tecovirimat (Tpoxx) for Treatment of Monkeypox Under an Investigational New Drug Protocol - United States, May-August 2022."
supports: SUPPORT
snippet: Tecovirimat (Tpoxx), however, is an antiviral drug that has
demonstrated efficacy in animal studies and is FDA-approved for treating
smallpox. Use of tecovirimat for treatment of monkeypox in the United
States is permitted only through an FDA-regulated Expanded Access
Investigational New Drug (EA-IND) mechanism.
explanation: The article supports the investigational use of tecovirimat
(TPOXX) for treating Monkeypox under an investigational new drug protocol.
- reference: PMID:36547989
reference_title: "Tecovirimat Treatment for Monkeypox Virus Keratouveitis."
supports: SUPPORT
snippet: Tecovirimat Treatment for Monkeypox Virus Keratouveitis.
explanation: The article specifically discusses the use of tecovirimat for
treating a form of Monkeypox, indicating ongoing investigative use.
- reference: PMID:36253931
reference_title: "Monkeypox treatment: Current evidence and future perspectives."
supports: SUPPORT
snippet: Brincidofovir and tecovirimat were the most studied medications
that got approval for smallpox treatment according to the Animal Rule. Due
to the conserved virology among Orthopoxviruses, available medications
might also be effective against monkeypox.
explanation: The text confirms that investigational treatments, particularly
tecovirimat (TPOXX), are considered for treating Monkeypox.
- reference: PMID:36470502
reference_title: "The use of antivirals in the treatment of human monkeypox outbreaks: a systematic review."
supports: SUPPORT
snippet: Tecovirimat was used in 61 individuals... Tecovirimat is the most
used and has proven beneficial in several aggravating cases.
explanation: The article provides individual patient data on the use of
tecovirimat as an investigational treatment for Monkeypox and summarizes
its efficacy and safety.
- reference: PMID:36746493
reference_title: "Human monkeypox: diagnosis and management."
supports: NO_EVIDENCE
snippet: ''
explanation: The provided literature does not include useful content to
verify the statement.
- reference: PMID:36851785
reference_title: "Fragment-Based Approaches Identified Tecovirimat-Competitive Novel Drug Candidate for Targeting the F13 Protein of the Monkeypox Virus."
supports: SUPPORT
snippet: In this study, we generated 800 compounds based on tecovirimat, an
FDA-approved drug that is efficacious at nanomolar quantities against
monkeypox
explanation: The article states that tecovirimat is effective at nanomolar
quantities against Monkeypox, supporting its use as investigational
therapy.
- reference: PMID:36897017
reference_title: "Repurposing of the antibiotic nitroxoline for the treatment of mpox."
supports: SUPPORT
snippet: The antiviral drugs tecovirimat, brincidofovir, and cidofovir are
considered for mpox (monkeypox) treatment despite a lack of clinical
evidence.
explanation: The article mentions tecovirimat as one of the investigational
treatments considered for monkeypox, supporting its use.
treatment_term:
preferred_term: antiviral agent therapy
term:
id: MAXO:0000168
label: antiviral agent therapy
- name: Vaccination
description: Smallpox vaccine (e.g., ACAM2000, Jynneos) may provide
cross-protection against monkeypox.
evidence:
- reference: PMID:36104166
reference_title: "Monkeypox in Patient Immunized with ACAM2000 Smallpox Vaccine During 2022 Outbreak."
supports: PARTIAL
snippet: We report a case of monkeypox in the United States in a patient who
had been vaccinated with ACAM2000 smallpox vaccine 8 years earlier.
Despite his vaccination status, he still contracted disease.
explanation: This case indicates that the patient contracted monkeypox
despite vaccination, suggesting limited or no cross-protection by the
ACAM2000 vaccine.
- reference: PMID:27768891
reference_title: "Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections."
supports: PARTIAL
snippet: Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause
severe human infections on an intermittent basis, and variola virus (VARV)
has potential for use as an agent of bioterror. Vaccinia immune globulin
(VIG) has been used therapeutically to treat severe orthopoxvirus
infections but is in short supply.
explanation: This reference mentions broader cross-protective immunity for
orthopoxviruses, including monkeypox, suggesting a potential for
cross-protection, though specifics about the smallpox vaccine's efficacy
aren't detailed.
- reference: PMID:35763248
reference_title: "Prevention and Treatment of Monkeypox."
supports: SUPPORT
snippet: Two vaccines are currently available, JYNNEOSTM (live, replication
incompetent vaccinia virus) and ACAM2000® (live, replication competent
vaccinia virus)
explanation: The presence of orthopoxvirus vaccines like ACAM2000 and
JYNNEOS indicates their consideration in the context of monkeypox
prevention, implying potential cross-protection.
- reference: PMID:37087871
reference_title: "Efficacy of the modified vaccinia Ankara virus vaccine and the replication-competent vaccine ACAM2000 in monkeypox prevention."
supports: SUPPORT
snippet: 'CONCLUSION: ACAM2000 and JYNNEOS vaccines have proven to be efficient
in preventing Mpox even though variations exist in their modes of action and
associated significant effects.'
explanation: Both the ACAM2000 and JYNNEOS vaccines show efficacy in
preventing monkeypox, supporting the statement regarding cross-protection.
- reference: PMID:36274490
reference_title: "Monkeypox virus vaccine evolution and global preparedness for vaccination."
supports: SUPPORT
snippet: It has been observed that smallpox vaccines can be used to protect
against MPX. The present article highlights the significant points and
various issues for vaccines and vaccinations that should be considered
related to MPX.
explanation: The use of smallpox vaccines for protection against monkeypox
is explicitly mentioned, supporting the potential for cross-protection.
treatment_term:
preferred_term: vaccination
term:
id: MAXO:0001017
label: vaccination
- name: Cidofovir
description: DNA polymerase inhibitor considered for severe cases.
notes: Repurposed antiviral targeting viral DNA polymerase; used
experimentally for severe MPXV infections
treatment_term:
preferred_term: antiviral agent therapy
term:
id: MAXO:0000168
label: antiviral agent therapy
- name: Brincidofovir
description: Lipid conjugate of cidofovir explored as oral antiviral
candidate.
notes: Oral prodrug formulation of cidofovir for improved bioavailability
treatment_term:
preferred_term: antiviral agent therapy
term:
id: MAXO:0000168
label: antiviral agent therapy
- name: Isolation and Infection Control
description: Preventing the spread through quarantine of infected individuals
and proper hygiene practices.
evidence:
- reference: PMID:36241815
reference_title: "Monkeypox: what do dental professionals need to know?"
supports: PARTIAL
snippet: Monkeypox is an infectious disease, characterised by a rash
affecting the skin and soft tissues, including the oral cavity.
explanation: The literature mentions the importance of infection control in
preventing the spread of monkeypox, particularly in dental settings.
treatment_term:
preferred_term: behavioral counseling
term:
id: MAXO:0000077
label: behavioral counseling
datasets:
# 2022 mpox outbreak strain transcriptomics
- accession: geo:GSE219036
title: Virological characterization of the 2022 outbreak-causing monkeypox
virus using human keratinocytes and colon organoids
description: >-
RNA-seq comparing 2022 outbreak strain to endemic MPXV clades (I, IIa, IIb)
in human keratinocytes and iPSC-derived colon organoids. Found MPXV
replication more productive in keratinocytes and unique hypoxia-related
gene expression triggered by 2022 outbreak strain.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: BULK_RNA_SEQ
sample_types:
- preferred_term: keratinocyte
cell_type_term:
preferred_term: keratinocyte
term:
id: CL:0000312
label: keratinocyte
sample_count: 24
conditions:
- mock infected
- MPXV clade I infected
- MPXV clade IIa infected
- MPXV clade IIb (2022 outbreak) infected
notes: >-
Key dataset for understanding 2022 outbreak strain virological
properties and host cell damage mechanisms. Identifies distinct
gene expression patterns between clades.
# MPXV replication in MK2 cells
- accession: geo:GSE21001
title: Infection of MK2 cells with monkeypox virus
description: >-
Microarray analysis of MK2 (monkey kidney) cells infected with
monkeypox virus at 3 and 7 hours post-infection to identify host
genes essential for viral replication. Examines how orthopoxvirus
alters host gene expression targeting immune responses.
organism:
preferred_term: rhesus macaque
term:
id: NCBITaxon:9544
label: Macaca mulatta
data_type: MICROARRAY
sample_types:
- preferred_term: kidney cell line
tissue_term:
preferred_term: kidney
term:
id: UBERON:0002113
label: kidney
sample_count: 9
conditions:
- mock infected control
- MPXV 3 hours post-infection
- MPXV 7 hours post-infection
platform: Affymetrix Rhesus Macaque Genome Array
notes: >-
Identifies host genes exploited for viral replication and humoral
immune response targeting. Important for understanding early viral
infection dynamics
review_notes: Enhanced with comprehensive pathophysiology mechanisms including
viral entry, lymphatic dissemination, hematogenous spread, viral factory
formation, EEV formation, immune evasion, and skin lesion pathogenesis. Added
cell type annotations (keratinocytes, Langerhans cells, dendritic cells,
monocytes, NK cells) with CL terms. Added biological processes (viral entry,
replication, assembly, interferon signaling, immune response) with GO terms.
Added anatomical locations (skin epidermis, lymph node, liver, spleen, blood,
mucosa) with UBERON terms. Added host genes involved in infection and immune
response (EGFR, STAT1, JAK2, IRF3, NFKB1, IL6, CXCL8, IFNG). Added phenotypes
for pustular rash, vesicles, and genital lesions. Added additional antiviral
treatments (cidofovir, brincidofovir). Based on deep research from Lu et al.
2023, Prompetchara et al. 2024, Parnian et al. 2024, and related recent
literature on mpox pathophysiology.
disease_term:
preferred_term: monkeypox
term:
id: MONDO:0002594
label: monkeypox
references:
- reference: DOI:10.1038/s41392-023-01675-2
title: 'Mpox (formerly monkeypox): pathogenesis, prevention and treatment'
findings: []
- reference: DOI:10.1101/2024.09.16.613292
title: MPXV Infects Human PBMCs in a Type I Interferon-Sensitive Manner
findings: []
- reference: DOI:10.1159/000540815
title: 'Innate Immune Response to MPOX Infection: Mechanisms and Immune Escape'
findings: []
- reference: DOI:10.12932/ap-111024-1945
title: 'Mpox global health emergency: Insights into the virus, immune responses,
and advancements in vaccines PART I: Insights into the virus and immune responses'
findings: []
- reference: DOI:10.3389/fcimb.2023.1196699
title: The prospective outcome of the monkeypox outbreak in 2022 and
characterization of monkeypox disease immunobiology
findings: []
- reference: DOI:10.3390/biomedicines12071457
title: 'The Re-Emergence of Mpox: Old Illness, Modern Challenges'
findings: []