This resource is in its pre-alpha development stage. Content is actively being curated and may be incomplete or subject to change.
0
Mappings
0
Definitions
0
Inheritance
7
Pathophysiology
0
Histopathology
15
Phenotypes
9
Genes
6
Treatments
2
Subtypes
0
Differentials
2
Datasets
0
Trials

Subtypes

2
West African Clade
Typically causes milder illness with lower mortality rates.
Show evidence (3 references)
PMID:36607751 SUPPORT
"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."
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.
PMID:36801633 SUPPORT
"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..."
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.
PMID:36604361 NO_EVIDENCE
"Monkeypox is a systemic exanthematous viral disease presenting with fever, lymphadenopathy, and vesicular rash."
This abstract provides an overview of monkeypox symptoms but does not distinguish between different clades or mention their severity or mortality rates.
Central African (Congo Basin) Clade
Generally associated with more severe clinical manifestations and higher mortality rates.
Show evidence (3 references)
PMID:36066176 SUPPORT
"Despite with a close genetic similarity between the two clades, the Central African strain is comparatively very virulent with high mortality."
The abstract clearly distinguishes the Central African clade as having higher virulence and mortality compared to the West African clade.
PMID:36328951 SUPPORT
"High fatality rates associated with monkeypox virus clade I also are a local and international concern."
Clade I corresponds to the Central African clade, and the abstract reports high fatality rates associated with it, supporting the statement.
PMID:20643162 SUPPORT
"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"
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.

Pathophysiology

7
Viral Entry and Initial Replication
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.
keratinocyte link Langerhans cell link dendritic cell link
viral entry into host cell link viral genome replication link
skin epidermis link mucosa link
Lymphatic Dissemination
Infected antigen-presenting cells (Langerhans cells, dendritic cells) migrate to draining lymph nodes where early viral amplification occurs, producing characteristic lymphadenopathy.
Langerhans cell link dendritic cell link
leukocyte migration link
lymph node link
Hematogenous Spread and Viremia
From lymph nodes, virus disseminates via bloodstream to lymphoid organs, liver, and other tissues. Monocytes can be productively infected, potentially mediating systemic spread.
monocyte link
virion attachment to host cell link
blood link spleen link liver link
Show evidence (1 reference)
PMID:37026012 SUPPORT
"Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs."
This snippet confirms that monkeypox virus multiplies at the site of entry and spreads into the bloodstream.
Viral Factory Formation
MPXV replicates entirely in the host cytoplasm, forming ER-associated viral factories (Guarnieri bodies) where genome replication and virion assembly occur.
viral genome replication link virion assembly link
Extracellular Enveloped Virion Formation
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.
viral budding via host ESCRT complex link viral release from host cell link
Immune Evasion
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.
natural killer cell link dendritic cell link
type I interferon signaling pathway link innate immune response link I-kappaB kinase/NF-kappaB signaling link
Skin Lesion Pathogenesis
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.
keratinocyte link
skin epidermis link
Show evidence (1 reference)
PMID:36253513 SUPPORT
"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."
This reference mentions that the virus is found in specific tissues after initial replication, which supports the idea that it spreads systemically.

Causal Graph

graph LR
    Secondary_Infections["Secondary Infections"]
    Scarring["Scarring"]
    Rash["Rash"]

    Rash --> Scarring
    Rash --> Secondary_Infections

    style Secondary_Infections fill:#fef3c7
    style Scarring fill:#fef3c7
    style Rash fill:#fef3c7

Phenotypes

15
Cardiovascular 2
Lymphadenopathy FREQUENT Lymphadenopathy (HP:0002716)
Swollen lymph nodes, particularly in the neck and groin
Conjunctivitis OCCASIONAL Conjunctivitis (HP:0000509)
Show evidence (3 references)
PMID:36216412 SUPPORT
"Ophthalmic manifestations may include preseptal cellulitis, conjunctivitis and keratitis."
The reference mentions conjunctivitis as one of the ophthalmic manifestations of monkeypox.
PMID:37405735 SUPPORT
"Mpox is an emerging zoonotic infection with potentially severe ocular and periocular consequences."
The reference discusses severe ocular consequences of monkeypox, implying various ophthalmic manifestations.
PMID:36986374 SUPPORT
"The aim of this meta-analysis was to estimate the global prevalence of ophthalmic manifestations in mpox patients."
The reference indicates that ophthalmic manifestations, including conjunctivitis, are present in monkeypox patients.
Digestive 2
Nausea OCCASIONAL Nausea (HP:0002018)
Vomiting OCCASIONAL Vomiting (HP:0002013)
Immune 3
Rash VERY_FREQUENT Skin rash (HP:0000988)
Rash typically starts on the face and spreads to other parts of the body
Sequelae: Scarring Secondary Infections
Show evidence (7 references)
PMID:36396927 SUPPORT
"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."
This reference confirms that rash is a common dermatologic manifestation of monkeypox.
PMID:36396927 SUPPORT
"Respiratory manifestations include nasal congestion and shortness of breath that may result in secondary bacterial infections."
This reference further mentions the potential for secondary infections.
PMID:35904894 SUPPORT
"Pleomorphic skin lesions appear ranging from macules, papules, vesicles, pustules, some of which may appear umbilicated before crusting over."
This reference supports the frequent occurrence of various types of rashes in monkeypox.
+ 4 more references
Pustule VERY_FREQUENT Pustular rash (HP:0033605)
Skin lesions progress through pustular stage before crusting
Secondary Infections FREQUENT Recurrent infections (HP:0002719)
Integument 1
Vesicles VERY_FREQUENT Skin vesicle (HP:0200037)
Vesicular stage precedes pustule formation
Metabolism 1
Fever VERY_FREQUENT Fever (HP:0001945)
Fever usually precedes the rash
Show evidence (1 reference)
PMID:35924502 SUPPORT
"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."
This reference also confirms that fever is a commonly observed systemic phenotype in monkeypox patients.
Musculoskeletal 1
Scarring FREQUENT Scarring (HP:0100699)
Nervous System 1
Headache FREQUENT Headache (HP:0002315)
Show evidence (2 references)
PMID:36554659 SUPPORT
"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."
This reference lists headache as a clinical characteristic of monkeypox, supporting the statement that headache is a frequent systemic symptom.
PMID:37043648 SUPPORT
"Several neurological complications have been reported with MPX and its vaccines that include but not limited to headaches, myalgia, encephalitis, and coma."
This reference mentions headaches as one of the neurological complications associated with monkeypox, supporting the statement.
Constitutional 2
Myalgia FREQUENT Myalgia (HP:0003326)
Muscle aches and pain are common
Show evidence (1 reference)
PMID:36396927 SUPPORT
"Other symptoms can include diarrhea, vomiting, myalgia, and backache."
The reference states that myalgia is a symptom that can occur in monkeypox patients, indicating it's a recognized phenotype.
Fatigue FREQUENT Fatigue (HP:0012378)
Show evidence (4 references)
PMID:36396927 NO_EVIDENCE
"Other symptoms can include diarrhea, vomiting, myalgia, and backache."
The abstract does not mention fatigue as a frequent systemic symptom of monkeypox.
PMID:36125794 NO_EVIDENCE
"known neurologic complications of monkeypox, which include headaches and mood disturbances, as well as rare presentations of encephalitis, transverse myelitis, and seizures."
The abstract does not mention fatigue as a frequent systemic symptom of monkeypox.
PMID:36716982 NO_EVIDENCE
"The most common symptoms were fever (89%) and chest pain (100%)."
The abstract does not mention fatigue as a frequent systemic symptom of monkeypox.
+ 1 more reference
Other 2
Sore Throat OCCASIONAL
Show evidence (2 references)
PMID:36174912 SUPPORT
"Clinical manifestations of the pharynx in human monkeypox."
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.
PMID:37721247 SUPPORT
"Respiratory manifestations and complications of monkeypox."
This reference indicates that respiratory manifestations, which can include sore throat, are part of monkeypox symptoms.
Genital Lesions FREQUENT
Common in 2022-2023 outbreak; mucocutaneous lesions in genital and anal areas
🧬

Genetic Associations

9
Monkeypox Virus Genome
Show evidence (3 references)
PMID:12083817 SUPPORT
"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."
The reference confirms that the monkeypox virus belongs to the Orthopoxvirus genus and details the structural features of its DNA genome.
PMID:38801573 SUPPORT
"The monkeypox virus is a part of the Poxviridae family, Orthopoxvirus genus, and is accountable for smallpox."
This reference reaffirms that the monkeypox virus belongs to the Orthopoxvirus genus and has a DNA-based genome.
PMID:37611023 SUPPORT
"Monkeypox is a double-stranded DNA virus with an envelope and is a member of the Poxviridae family's Orthopoxvirus genus."
This reference confirms the genetic features and classification of the monkeypox virus as specified in the statement.
EGFR (Host receptor hijacked for viral spread)
STAT1 (Downregulated during infection)
JAK2 (Downregulated during infection)
IRF3 (Antagonized by viral proteins)
NFKB1 (Antagonized by viral proteins)
IL6 (Upregulated during infection)
CXCL8 (Upregulated during infection)
IFNG (Dysregulated during infection)
💊

Treatments

6
Supportive Care MAXO:0000950
Management of symptoms including fever, pain, and dehydration.
Show evidence (3 references)
PMID:37403493 SUPPORT
"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"
The document emphasizes how supportive care is central to the management of symptoms, including fever.
PMID:29231870 SUPPORT
"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..."
This reference highlights the importance of supportive care for hydration and managing symptoms.
PMID:36342045 SUPPORT
"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."
This supports the role of supportive care in managing mild symptoms, including fever and pain.
Antiviral Therapy MAXO:0000168
Investigational treatments such as tecovirimat (TPOXX).
Show evidence (7 references)
PMID:36107794 SUPPORT
"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..."
The article supports the investigational use of tecovirimat (TPOXX) for treating Monkeypox under an investigational new drug protocol.
PMID:36547989 SUPPORT
"Tecovirimat Treatment for Monkeypox Virus Keratouveitis."
The article specifically discusses the use of tecovirimat for treating a form of Monkeypox, indicating ongoing investigative use.
PMID:36253931 SUPPORT
"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."
The text confirms that investigational treatments, particularly tecovirimat (TPOXX), are considered for treating Monkeypox.
+ 4 more references
Vaccination MAXO:0001017
Smallpox vaccine (e.g., ACAM2000, Jynneos) may provide cross-protection against monkeypox.
Show evidence (5 references)
PMID:36104166 PARTIAL
"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."
This case indicates that the patient contracted monkeypox despite vaccination, suggesting limited or no cross-protection by the ACAM2000 vaccine.
PMID:27768891 PARTIAL
"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..."
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.
PMID:35763248 SUPPORT
"Two vaccines are currently available, JYNNEOSTM (live, replication incompetent vaccinia virus) and ACAM2000® (live, replication competent vaccinia virus)"
The presence of orthopoxvirus vaccines like ACAM2000 and JYNNEOS indicates their consideration in the context of monkeypox prevention, implying potential cross-protection.
+ 2 more references
Cidofovir MAXO:0000168
DNA polymerase inhibitor considered for severe cases.
Brincidofovir MAXO:0000168
Lipid conjugate of cidofovir explored as oral antiviral candidate.
Isolation and Infection Control MAXO:0000077
Preventing the spread through quarantine of infected individuals and proper hygiene practices.
Show evidence (1 reference)
PMID:36241815 PARTIAL
"Monkeypox is an infectious disease, characterised by a rash affecting the skin and soft tissues, including the oral cavity."
The literature mentions the importance of infection control in preventing the spread of monkeypox, particularly in dental settings.
🔬

Biochemical Markers

2
Monkeypox Virus PCR (Positive)
Context: Diagnostic test to confirm the presence of the virus
Show evidence (5 references)
PMID:36529507 SUPPORT
"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..."
The statement is supported as the document states that PCR is the laboratory test of choice to confirm monkeypox virus infection.
PMID:37646742 SUPPORT
"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)."
The use of reverse transcriptase PCR (RT-PCR) is mentioned as part of their diagnostic methodology for monkeypox.
PMID:36052723 SUPPORT
"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..."
The document discusses the use of PCR for detecting monkeypox virus DNA in clinical samples and correlating it with infectivity.
+ 2 more references
Serology for Orthopoxvirus Antibodies (Positive)
Context: Indicates exposure to or vaccination against orthopoxviruses
Show evidence (4 references)
PMID:18165539 SUPPORT
"Titers of IgM and IgG to OPX were assessed using an enzyme-linked immunosorbent assay."
The study assessed the presence of antibodies against orthopoxviruses, which indicates exposure to or vaccination against these viruses.
PMID:27768891 SUPPORT
"We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects."
This research identifies antibodies specific to orthopoxviruses, which would be detectable in serological tests indicating exposure or vaccination.
PMID:23973323 SUPPORT
"A serological survey was conducted in a Brazilian laboratory to evaluate staff exposure to orthopoxviruses (OPVs)."
The study shows that serology for orthopoxvirus antibodies is used to determine exposure to the viruses, which aligns with the given statement.
+ 1 more reference
📊

Related Datasets

2
Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids geo:GSE219036
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.
human BULK RNA SEQ n=24
keratinocyte link
Conditions: mock infected MPXV clade I infected MPXV clade IIa infected MPXV clade IIb (2022 outbreak) infected
Key dataset for understanding 2022 outbreak strain virological properties and host cell damage mechanisms. Identifies distinct gene expression patterns between clades.
Infection of MK2 cells with monkeypox virus geo:GSE21001
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.
rhesus macaque MICROARRAY n=9 Affymetrix Rhesus Macaque Genome Array
kidney cell line
Conditions: mock infected control MPXV 3 hours post-infection MPXV 7 hours post-infection
Identifies host genes exploited for viral replication and humoral immune response targeting. Important for understanding early viral infection dynamics
{ }

Source YAML

click to show
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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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: viral 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
    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 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: I-kappaB kinase/NF-kappaB signaling
  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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    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
    supports: NO_EVIDENCE
    snippet: ''
    explanation: The provided literature does not include useful content to
      verify the statement.
  - reference: PMID:36851785
    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
    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
    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
    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
    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
    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
    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
    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: []