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Chickenpox

Disease Pathophysiology Research Template

2026-02-18
Falcon MONDO:0005700 Model: Edison Scientific Literature 30 citations

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Pathophysiology Research Template

Target Disease

  • Disease Name: Chickenpox
  • MONDO ID: (if available)
  • Category: Infectious

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Chickenpox. Focus on the molecular and cellular mechanisms underlying disease progression.

Required Information

1. Core Pathophysiology

  • What are the primary pathophysiological mechanisms?
  • What molecular pathways are dysregulated?
  • What cellular processes are affected?

2. Key Molecular Players

  • Genes/Proteins: Which genes are causally involved or implicated?
  • Chemical Entities: What metabolites, drugs, or small molecules are relevant?
  • Cell Types: Which cell types are primarily affected?
  • Anatomical Locations: Which tissues/organs are involved?

3. Biological Processes (for GO annotation)

  • What biological processes (GO terms) are disrupted?
  • Consider: signaling pathways, metabolic processes, cellular responses, transport, etc.

4. Cellular Components

  • Where in the cell do key processes occur?
  • Consider: organelles, membrane compartments, extracellular space, etc.

5. Disease Progression

  • What is the sequence of events from initial trigger to clinical manifestation?
  • Are there distinct stages or phases?

6. Phenotypic Manifestations

  • What are the key clinical phenotypes?
  • How do they relate to the underlying mechanisms?

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes where possible to support key statements

Output Format

Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs

Title: Pathophysiology of Chickenpox (Varicella) Caused by Varicella‑Zoster Virus (VZV): Molecular and Cellular Mechanisms (2023–2024 Evidence Synthesis)

Disease identifiers - Disease: Chickenpox (varicella; primary VZV infection) - Category: Infectious disease (human alphaherpesvirus) - MONDO: Not retrieved from the provided sources in this run (not reported in the accessed texts).

  1. Key concepts and definitions (current understanding)

1.1 Etiologic agent and lifecycle states Varicella is the clinical syndrome of primary infection with varicella‑zoster virus (VZV), a human neurotropic alphaherpesvirus that has a biphasic lifecycle: a lytic (productive) phase in permissive tissues and a latent phase in sensory ganglia with highly restricted transcription. (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2)

During primary infection, VZV replicates in T cells, producing viremia that disseminates virus to skin and other sites; after resolution, VZV establishes lifelong latency in sensory neurons (dorsal root ganglia and trigeminal ganglia are emphasized). (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2)

1.2 Clinically relevant “pathophysiology” for chickenpox In chickenpox, the pathophysiologic hallmark is systemic dissemination (viremia) from a respiratory entry site to the skin, resulting in widespread vesicular lesions; concurrently, VZV gains access to peripheral nerves and sensory ganglia where latent infection is established. (beloushi2024congenitalandperinatal pages 18-19, beloushi2024congenitalandperinatal media 2d139972)

  1. Core pathophysiology (molecular/cellular mechanisms)

2.1 Entry and early replication: upper airway → lymphoid tissues Recent review-level synthesis describes VZV entering via the upper respiratory tract, replicating in mucosa and lymphoid tissues (including tonsils), and then disseminating via infected T cells in the bloodstream. (beloushi2024congenitalandperinatal pages 18-19, beloushi2024congenitalandperinatal media 2d139972)

Consistent with this, a 2024 review focused on vaccine-related neurologic adverse events highlights VZV tropism for tonsillar CD4+ T lymphocytes that express activation/memory and skin-homing features, supporting a mechanism in which infected T cells act as vehicles for systemic spread toward skin. (ramachandran2024seriousneurologicaladverse pages 11-12)

2.2 Viremia and dissemination to skin and nerves (cellular trafficking model) A 2024 Nature Communications paper reiterates that, in primary infection, VZV replication in T cells “leads to viremia and dissemination to various organs like skin, causing chickenpox,” with subsequent establishment of latency in dorsal root and trigeminal ganglia. (yang2024identificationandcharacterization pages 1-2)

2.3 Skin infection and lesion formation: productive infection, barrier disruption, and fusogenic spread VZV productive infection in skin yields vesicular lesions and disrupts normal cutaneous architecture, which contributes to susceptibility to secondary bacterial superinfection. (purohit2024varicellazostervirus pages 1-2)

Mechanistically, VZV envelope glycoproteins are central to entry and cell-to-cell spread in skin: coexpression of gB with gE (and, separately, gH with gL) promotes fusion and syncytium formation; gE is required for viral replication and is functionally supported by gI, with a gE:gI complex implicated in endocytosis; gH/gL is linked to fusion and skin tropism; and gM supports cell-to-cell spread. (xiran2024preliminaryinvestigationand pages 11-11)

2.4 Innate immune dysregulation: type I interferon (IFN-I) antagonism and “immune evasion before entry” via extracellular vesicles A 2024 Journal of Virology study details multiple VZV proteins that antagonize IFN-I signaling at the IRF3 node: ORF61p induces IRF3 ubiquitination and proteasomal degradation; ORF47p blocks IRF3 Ser396 phosphorylation and downstream transcription of IFNβ and ISG15; and the major immediate early transactivator IE-62 inhibits IRF3 phosphorylation in a TBK1-independent fashion. (niemeyer2024suppressionofthe pages 1-2)

The same work proposes a previously undescribed mechanism in which non-infectious small extracellular vesicles released from VZV-infected sensory neurons contain viral and host immunosuppressive cargo and can suppress IFN-I responses in recipient cells, potentially contributing to distant pathologies outside the initial infection focus. This reframes VZV pathogenesis as potentially involving systemic immune modulation by non-virion particles. (niemeyer2024suppressionofthe pages 1-2)

2.5 Antigen presentation and cellular effector dysfunction (adaptive and innate-like T cells) Evidence from a 2024 PLOS Pathogens study highlights that VZV productively infects and/or functionally disrupts multiple immune subsets (monocytes, dendritic cells, conventional T cells, NK cells), and encodes immune-evasion strategies including downregulation of MHC-I, MHC-II, and NK-cell activating ligands—mechanisms that can impair cytotoxic recognition and antigen presentation during dissemination. (purohit2024varicellazostervirus pages 1-2)

That study also adds a specific immunologic angle: VZV “profoundly impairs” MAIT cell activation and diminishes polyfunctional effector outputs, supporting an additional layer of immune evasion at barrier sites and in circulation. (purohit2024varicellazostervirus pages 1-2)

Complementing these immune findings, a 2024 hiPSC-derived neurospheroid model shows that VZV infection fails to trigger a robust type I IFN response and instead suppresses IFN signaling and antigen-presentation programs, including reduced IL-6 and CXCL10 production, failure to upregulate antiviral ISGs (MX1, IFIT2, ISG15), and reduced expression of CD74 (invariant chain in MHC-II antigen presentation). (govaerts2024varicellazostervirusrecapitulates pages 1-2)

2.6 Neuronal infection and establishment of latency (molecular state) Primary infection seeds sensory ganglia for lifelong latency. Latency is characterized by restricted viral transcription; a 2024 Nature Communications paper notes VZV latency-associated transcripts (VLTs) and VLT–ORF63 fusion transcripts as prominent features of latency-associated expression patterns, while most lytic genes are silent. (yang2024identificationandcharacterization pages 1-2)

A 2023 Viruses review (focused on reactivation) reinforces the restricted nature of VZV latency transcription and highlights emerging transcriptomic observations (including VLT-related transcripts) and host immune factors affecting control. (kennedy2023thespectrumof pages 1-2)

  1. Key molecular players (entities for knowledge base annotation)

3.1 Viral genes/proteins (VZV; HHV-3) Key VZV immune evasion/latency regulators - ORF61p (IE protein; IRF3 antagonism) (niemeyer2024suppressionofthe pages 1-2) - ORF47p (kinase; blocks IRF3 Ser396 phosphorylation; IFNβ/ISG15 suppression) (niemeyer2024suppressionofthe pages 1-2) - IE-62 / ORF62 (major transactivator; inhibits IRF3 phosphorylation) (niemeyer2024suppressionofthe pages 1-2) - ORF63 and VLT / VLT–ORF63 fusion transcripts (latency-associated expression) (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2)

Entry/spread and skin tropism determinants (envelope) - gB, gE, gI, gH, gL, gM, gC (fusion, cell-to-cell spread, skin tropism, virulence/attenuation determinants) (xiran2024preliminaryinvestigationand pages 11-11)

Other loci noted in surveillance/pathogenesis context - dUTPase, ORF9A (growth/syncytia/virulence-related loci discussed in glycoprotein-focused surveillance review) (xiran2024preliminaryinvestigationand pages 11-11)

3.2 Host genes/proteins and pathways (HGNC symbols where applicable) Innate sensing/IFN axis - IRF3 (targeted by VZV ORF61p and ORF47p; phosphorylation and stability altered) (niemeyer2024suppressionofthe pages 1-2) - TBK1 (referenced in IE62 mechanism as TBK1-independent inhibition of IRF3 phosphorylation) (niemeyer2024suppressionofthe pages 1-2) - IFNB1 (IFNβ; downstream transcription impacted) (niemeyer2024suppressionofthe pages 1-2) - ISG15, MX1, IFIT2 (IFN-stimulated genes; suppressed in neural model; ISG15 also downstream of ORF47 effect) (niemeyer2024suppressionofthe pages 1-2, govaerts2024varicellazostervirusrecapitulates pages 1-2)

Antigen presentation and inflammatory mediators - CD74 (MHC-II invariant chain; reduced in neurospheroid infection) (govaerts2024varicellazostervirusrecapitulates pages 1-2) - IL6, CXCL10 (suppressed cytokines/chemokines in neural model) (govaerts2024varicellazostervirusrecapitulates pages 1-2) - MHC-I and MHC-II (downregulated by VZV as immune evasion strategy) (purohit2024varicellazostervirus pages 1-2)

Host susceptibility/immune control hints - STAT5B (noted in reactivation context as relevant to immune control) (kennedy2023thespectrumof pages 1-2) - RNA polymerase III (POL III; noted as a DNA-sensing component relevant to VZV) (kennedy2023thespectrumof pages 1-2)

3.3 Cell types (Cell Ontology-style labels) - Tonsillar CD4+ T lymphocytes with activation/memory and skin-homing phenotype (vehicle for dissemination) (ramachandran2024seriousneurologicaladverse pages 11-12) - Peripheral blood T cells (replication/viremia vehicle) (yang2024identificationandcharacterization pages 1-2) - Monocytes; dendritic cells; NK cells (infected/disrupted; immune evasion targets) (purohit2024varicellazostervirus pages 1-2) - MAIT cells (unconventional T cells; functionally impaired) (purohit2024varicellazostervirus pages 1-2) - Sensory neurons (site of lifelong latency; source of VZV-associated extracellular vesicles in neuron model) (niemeyer2024suppressionofthe pages 1-2, yang2024identificationandcharacterization pages 1-2) - Astrocytes/neurons in 3D neural tissue models (IFN/antigen presentation suppression demonstrated) (govaerts2024varicellazostervirusrecapitulates pages 1-2)

3.4 Anatomical locations (UBERON-style labels) - Upper respiratory mucosa; tonsils/lymphoid tissues (entry and early replication) (beloushi2024congenitalandperinatal pages 18-19, beloushi2024congenitalandperinatal media 2d139972) - Bloodstream (T-cell viremia/dissemination) (yang2024identificationandcharacterization pages 1-2, beloushi2024congenitalandperinatal pages 18-19) - Skin (site of productive infection and vesicular rash) (purohit2024varicellazostervirus pages 1-2, yang2024identificationandcharacterization pages 1-2) - Peripheral nerves; dorsal root ganglia; trigeminal ganglia; autonomic ganglia (neuroinvasion/latency sites) (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2, beloushi2024congenitalandperinatal pages 18-19)

3.5 Chemical entities / interventions (CHEBI-style where possible) - Acyclovir (antiviral therapy used in real-world outbreak/pregnancy cases; also referenced in CNS disease management contexts) (graham2024varicellaoutbreakamong pages 2-4) - Valacyclovir (antiviral used clinically; referenced in outbreak pregnancy treatment context) (graham2024varicellaoutbreakamong pages 2-4) - Varicella-containing vaccines (public health implementation; effectiveness noted in outbreak response) (graham2024varicellaoutbreakamong pages 1-2, graham2024varicellaoutbreakamong pages 2-4)

  1. Biological processes (GO-style) and cellular components (GO-CC-style)

4.1 Biological processes disrupted (examples) - Viral entry into host cell; viral membrane fusion and syncytium formation (gB/gE; gH/gL) (xiran2024preliminaryinvestigationand pages 11-11) - Viral dissemination via leukocyte-mediated transport (T-cell viremia model) (ramachandran2024seriousneurologicaladverse pages 11-12, yang2024identificationandcharacterization pages 1-2) - Negative regulation of type I interferon production and signaling (IRF3 antagonism; suppression of ISGs) (niemeyer2024suppressionofthe pages 1-2, govaerts2024varicellazostervirusrecapitulates pages 1-2) - Antigen processing and presentation via MHC class I and MHC class II (downregulation; CD74 reduction) (purohit2024varicellazostervirus pages 1-2, govaerts2024varicellazostervirusrecapitulates pages 1-2) - Cytokine-mediated signaling (IL-6, CXCL10 suppression) (govaerts2024varicellazostervirusrecapitulates pages 1-2) - Establishment of viral latency in host cell (VLTs; latency in ganglia) (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2)

4.2 Cellular components (where key processes occur) - Plasma membrane and fusion machinery (glycoprotein-driven cell-cell fusion) (xiran2024preliminaryinvestigationand pages 11-11) - Endocytic vesicles (gE:gI endocytosis association) (xiran2024preliminaryinvestigationand pages 11-11) - Nucleus (IRF3 phosphorylation/transcriptional control; VZV lytic transcription program) (niemeyer2024suppressionofthe pages 1-2, yang2024identificationandcharacterization pages 1-2) - Proteasome (IRF3 proteasomal degradation driven by ORF61p) (niemeyer2024suppressionofthe pages 1-2) - Extracellular vesicles / small extracellular vesicles (non-infectious immunomodulatory sEVs) (niemeyer2024suppressionofthe pages 1-2) - Stress granules (formed during long-term VZV infection in neurospheroids) (govaerts2024varicellazostervirusrecapitulates pages 1-2)

  1. Disease progression: sequence of events and phases (mechanism-linked)

5.1 Stages (canonical model supported by 2024 sources) Stage 1: Exposure and incubation - Incubation is reported as 10–21 days (average ~14 days). (beloushi2024congenitalandperinatal pages 18-19, graham2024varicellaoutbreakamong pages 1-2)

Stage 2: Primary replication and lymphoid amplification - Entry via upper respiratory tract with replication in mucosa and lymphoid tissue (tonsils). (beloushi2024congenitalandperinatal pages 18-19, beloushi2024congenitalandperinatal media 2d139972)

Stage 3: Cell-associated viremia and immune evasion - Dissemination occurs via infected T cells in blood (T-cell replication → viremia → seeding of skin). (yang2024identificationandcharacterization pages 1-2, beloushi2024congenitalandperinatal pages 18-19) - Concurrently, VZV antagonizes IFN-I signaling (ORF61p/ORF47p/IE62 targeting IRF3) and impairs antigen presentation (MHC-I/MHC-II downregulation; CD74 reduction), limiting immune containment during dissemination. (niemeyer2024suppressionofthe pages 1-2, purohit2024varicellazostervirus pages 1-2, govaerts2024varicellazostervirusrecapitulates pages 1-2)

Stage 4: Cutaneous infection and rash - Productive infection in skin produces vesicular lesions and barrier disruption; fusogenic glycoprotein machinery (gB/gE; gH/gL) supports cell-to-cell spread. (purohit2024varicellazostervirus pages 1-2, xiran2024preliminaryinvestigationand pages 11-11)

Stage 5: Neuroinvasion and latency establishment - VZV gains access to peripheral nerves and sensory ganglia during primary infection, establishing lifelong neuronal latency with restricted expression patterns (VLTs; VLT–ORF63 fusion). (yang2024identificationandcharacterization pages 1-2, beloushi2024congenitalandperinatal pages 18-19)

5.2 Infectious period and lesion kinetics (clinically relevant physiology) - Infectiousness begins ~24–48 hours before rash onset and continues until lesions crust (reported ~4–5 days). (beloushi2024congenitalandperinatal pages 18-19) - Lesions are described as taking ~4 days to crust in a 2024 review. (beloushi2024congenitalandperinatal pages 18-19)

  1. Phenotypic manifestations (HPO-style mapping; mechanism links)

Core phenotypes - Generalized vesicular rash / varicella exanthem (skin infection and spread; fusogenic glycoproteins; barrier disruption) (purohit2024varicellazostervirus pages 1-2, xiran2024preliminaryinvestigationand pages 11-11) - Pruritus (not mechanistically dissected in these sources; noted in clinical descriptions) (graham2024varicellaoutbreakamong pages 1-2) - Fever (consistent with systemic infection/viremia; referenced in clinical staging literature) (beloushi2024congenitalandperinatal pages 18-19)

Complication phenotypes (selected, supported by 2024 outbreak data) - Pneumonia, encephalitis, bacteremia, secondary bacterial skin superinfection as reasons for hospitalization during a large outbreak (supports real-world relevance of barrier disruption and systemic dissemination). (graham2024varicellaoutbreakamong pages 2-4)

  1. Recent developments and latest research (prioritizing 2023–2024)

7.1 Immune evasion expanded beyond infected cells: extracellular vesicle model (2024) A major conceptual development is the demonstration that non-infectious small extracellular vesicles from VZV-infected sensory neurons can suppress type I interferon responses in recipient cells. This suggests VZV pathogenesis may involve systemic immunomodulation at a distance, not solely direct infection at sites of disease. (niemeyer2024suppressionofthe pages 1-2)

7.2 Viral circRNAs and lytic/latent transcript complexity (2024) Deep sequencing identifies extensive VZV circular RNAs during lytic infection and VLT-like circRNAs, adding a new regulatory layer to VZV gene expression; although the studied paper emphasizes lytic infection and antiviral sensitivity, it also reiterates T-cell-mediated dissemination and defines latency-associated transcript features. (yang2024identificationandcharacterization pages 1-2)

7.3 Human neural 3D models showing IFN and antigen-presentation suppression (2024) A matured hiPSC-derived neurospheroid model demonstrates that VZV infection is “immunologically ignored” relative to a positive-control virus, with suppression of IFN signaling genes and antigen presentation (e.g., reduced CD74), and emergence of stress granules and cellular integrity disruption with long-term infection. (govaerts2024varicellazostervirusrecapitulates pages 1-2)

7.4 Immune-cell subset specific impairment: MAIT cells (2024) MAIT cells, an unconventional T-cell subset important in antimicrobial responses, are shown to have impaired activation, cytokine production, and cytolytic potential following VZV infection/exposure, supporting a targeted immune evasion strategy affecting polyfunctional effector responses. (purohit2024varicellazostervirus pages 1-2)

  1. Current applications and real-world implementations

8.1 Vaccination as primary prevention (outbreak control) A CDC MMWR report documents a large varicella outbreak in New York City among recent arrivals (Sept 2022–Mar 2024) with 873 outbreak-associated cases and 28 hospitalizations. Control measures included administration of ~27,000 varicella-containing vaccine doses, and documented immunity among children increased from 28% (Dec 2022) to >80% (Feb 2023), illustrating real-world implementation of vaccination campaigns in congregate settings. (graham2024varicellaoutbreakamong pages 1-2, graham2024varicellaoutbreakamong pages 2-4)

8.2 Antiviral treatment (clinical management, including pregnancy) In the same outbreak report, pregnant persons with varicella were treated with acyclovir, reflecting standard antiviral implementation in higher-risk groups (and emphasizing the clinical relevance of limiting viral replication/dissemination). (graham2024varicellaoutbreakamong pages 2-4)

  1. Relevant statistics and data (recent studies)

9.1 Burden and epidemiology A 2024 review reports (as background burden estimates) approximately 4 million varicella cases per year in the USA, 100–150 deaths, and >100,000 hospital admissions; it also states that by age 15, up to 80–98% (up to ~90%) of individuals in Europe/North America have been infected, while estimates in low/middle-income countries range from 50–90%. (beloushi2024congenitalandperinatal pages 18-19)

9.2 Outbreak data (2022–2024) In the NYC outbreak, 91.9% of cases lacked documentation of varicella vaccination at symptom onset, and no deaths were reported. (graham2024varicellaoutbreakamong pages 1-2, graham2024varicellaoutbreakamong pages 2-4)

9.3 Regional surveillance example (China, 2010–2024) A 2024 Scientific Reports study using surveillance data from Jilin Province, China reports incidence peaks of 30.5 per 100,000 (2009) and 33.89 per 100,000 (2019), and notes sporadic fatalities in some years; the study also describes molecular sampling criteria (specimens with PCR Ct <25 selected for sequencing) and sequencing counts (92 collected, 38 sequenced). (xiran2024preliminaryinvestigationand pages 2-3, xiran2024preliminaryinvestigationand pages 1-2)

  1. Expert opinions and analysis (authoritative interpretations from 2023–2024 sources)

  2. VZV pathogenesis is increasingly understood as requiring efficient early immune evasion for systemic spread; current work emphasizes that “mechanisms of immune evasion prior to virion entry” have been incompletely elucidated and can involve non-infectious extracellular vesicles, broadening expert models of how VZV may contribute to remote complications. (niemeyer2024suppressionofthe pages 1-2)

  3. Reviews and primary studies converge on a cell-associated dissemination model—particularly T-cell–mediated viremia—to explain how a respiratory entry event produces widespread skin disease and simultaneously seeds ganglionic latency. (ramachandran2024seriousneurologicaladverse pages 11-12, yang2024identificationandcharacterization pages 1-2, beloushi2024congenitalandperinatal pages 18-19)

  4. Evidence-backed “Pathophysiology description” (knowledge-base ready)

Chickenpox (varicella) is caused by primary infection with VZV. The current evidence-supported model describes entry via the upper respiratory tract, with early replication in mucosa and lymphoid tissue including tonsils, followed by cell-associated viremia in which infected T cells traffic virus through the bloodstream. Dissemination seeds productive infection in skin, where glycoprotein-mediated cell-to-cell spread and fusion support lesion formation and barrier disruption, predisposing to secondary bacterial superinfection. Concurrently, VZV employs immune evasion mechanisms that inhibit type I interferon induction (ORF61p, ORF47p, and IE62 targeting IRF3 signaling and downstream ISGs) and reduce antigen presentation (MHC-I/MHC-II pathway impacts and CD74 reduction), and it can suppress unconventional T-cell effector programs (MAIT cells). During primary infection, VZV also gains access to peripheral nerves and sensory ganglia, establishing lifelong neuronal latency characterized by restricted transcription dominated by latency-associated transcripts such as VLTs and VLT–ORF63 fusion transcripts. (beloushi2024congenitalandperinatal pages 18-19, beloushi2024congenitalandperinatal media 2d139972, yang2024identificationandcharacterization pages 1-2, xiran2024preliminaryinvestigationand pages 11-11, purohit2024varicellazostervirus pages 1-2, niemeyer2024suppressionofthe pages 1-2, govaerts2024varicellazostervirusrecapitulates pages 1-2, kennedy2023thespectrumof pages 1-2)

  1. Ontology-focused annotation tables (seed set)

12.1 Gene/protein annotations (HGNC for host; VZV ORFs for viral) Host (HGNC symbols) - IRF3 — targeted for degradation and phosphorylation blockade (niemeyer2024suppressionofthe pages 1-2) - TBK1 — referenced in IE62 inhibition mechanism (niemeyer2024suppressionofthe pages 1-2) - IFNB1 — downstream transcription inhibited (niemeyer2024suppressionofthe pages 1-2) - ISG15, MX1, IFIT2 — suppressed ISG program in neural model (govaerts2024varicellazostervirusrecapitulates pages 1-2) - CD74 — reduced expression (MHC-II pathway) (govaerts2024varicellazostervirusrecapitulates pages 1-2) - IL6, CXCL10 — suppressed cytokine/chemokine production (govaerts2024varicellazostervirusrecapitulates pages 1-2)

Viral (VZV) - ORF61p, ORF47p, ORF62 (IE62) — IFN-I antagonism (niemeyer2024suppressionofthe pages 1-2) - ORF63; VLT; VLT–ORF63 — latency-associated expression (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2) - gB/gE/gI/gH/gL/gM/gC — entry/fusion/cell-to-cell spread/skin tropism (xiran2024preliminaryinvestigationand pages 11-11)

12.2 Biological processes (GO BP; suggested) - Type I interferon signaling pathway; negative regulation of type I interferon production (niemeyer2024suppressionofthe pages 1-2, govaerts2024varicellazostervirusrecapitulates pages 1-2) - Antigen processing and presentation of peptide antigen via MHC class I / class II (purohit2024varicellazostervirus pages 1-2, govaerts2024varicellazostervirusrecapitulates pages 1-2) - Viral entry into host cell; membrane fusion; cell-cell fusion (xiran2024preliminaryinvestigationand pages 11-11) - Leukocyte-mediated viral dissemination (T cell–associated viremia; suggested mapping) (ramachandran2024seriousneurologicaladverse pages 11-12, yang2024identificationandcharacterization pages 1-2) - Establishment of viral latency in host cell (sensory neuron) (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2)

12.3 Cellular components (GO CC; suggested) - Proteasome complex (IRF3 degradation) (niemeyer2024suppressionofthe pages 1-2) - Extracellular vesicle / small extracellular vesicle (sEV-mediated IFN suppression) (niemeyer2024suppressionofthe pages 1-2) - Stress granule (VZV-associated stress granules in long-term neural infection) (govaerts2024varicellazostervirusrecapitulates pages 1-2) - MHC class II protein complex (CD74/invariant chain association) (govaerts2024varicellazostervirusrecapitulates pages 1-2)

12.4 Cell type involvement (CL; suggested) - CD4-positive, alpha-beta T cell (tonsillar CD4+; dissemination vehicle) (ramachandran2024seriousneurologicaladverse pages 11-12) - Mucosal-associated invariant T cell (MAIT cell) (purohit2024varicellazostervirus pages 1-2) - Natural killer cell; dendritic cell; monocyte (immune disruption/evasion) (purohit2024varicellazostervirus pages 1-2) - Sensory neuron (latency reservoir) (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2)

12.5 Anatomical locations (UBERON; suggested) - Upper respiratory tract mucosa; tonsil; lymphoid tissue (early replication) (beloushi2024congenitalandperinatal pages 18-19, beloushi2024congenitalandperinatal media 2d139972) - Skin (cutaneous lesions) (purohit2024varicellazostervirus pages 1-2, yang2024identificationandcharacterization pages 1-2) - Dorsal root ganglion; trigeminal ganglion; autonomic ganglion (latency sites) (yang2024identificationandcharacterization pages 1-2, kennedy2023thespectrumof pages 1-2, beloushi2024congenitalandperinatal pages 18-19)

12.6 Phenotype associations (HPO; suggested) - Vesicular rash / exanthem (skin lytic infection) (purohit2024varicellazostervirus pages 1-2, graham2024varicellaoutbreakamong pages 1-2) - Secondary bacterial skin infection (barrier disruption context) (purohit2024varicellazostervirus pages 1-2, graham2024varicellaoutbreakamong pages 2-4) - Pneumonia; encephalitis (severe complications documented in outbreak hospitalizations) (graham2024varicellaoutbreakamong pages 2-4)

  1. Evidence items (with publication dates and URLs; PMIDs) The accessed evidence sources in this run predominantly provide DOIs/URLs; PMIDs were not present in the retrieved excerpts and therefore cannot be reliably reported here.

Key 2024–2023 sources used - Al Beloushi et al. Viruses. 2024-10. https://doi.org/10.3390/v16111698 (beloushi2024congenitalandperinatal pages 18-19, beloushi2024congenitalandperinatal media 2d139972) - Graham et al. MMWR. 2024-05. https://doi.org/10.15585/mmwr.mm7321a1 (graham2024varicellaoutbreakamong pages 1-2, graham2024varicellaoutbreakamong pages 2-4) - Niemeyer et al. Journal of Virology. 2024-08. https://doi.org/10.1128/jvi.00848-24 (niemeyer2024suppressionofthe pages 1-2) - Purohit et al. PLOS Pathogens. 2024-08. https://doi.org/10.1371/journal.ppat.1012372 (purohit2024varicellazostervirus pages 1-2) - Yang et al. Nature Communications. 2024-06. https://doi.org/10.1038/s41467-024-49112-4 (yang2024identificationandcharacterization pages 1-2) - Govaerts et al. Frontiers in Immunology. 2024-09. https://doi.org/10.3389/fimmu.2024.1458967 (govaerts2024varicellazostervirusrecapitulates pages 1-2) - Ramachandran & Grose. Reviews in Medical Virology. 2024-04. https://doi.org/10.1002/rmv.2538 (ramachandran2024seriousneurologicaladverse pages 11-12) - Kennedy. Viruses. 2023-07. https://doi.org/10.3390/v15081663 (kennedy2023thespectrumof pages 1-2) - Xiran et al. Scientific Reports. 2024-10. https://doi.org/10.1038/s41598-024-73072-w (xiran2024preliminaryinvestigationand pages 11-11, xiran2024preliminaryinvestigationand pages 2-3, xiran2024preliminaryinvestigationand pages 1-2)

References

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  11. (graham2024varicellaoutbreakamong pages 1-2): Krishika A. Graham, Robert J. Arciuolo, Olivia Matalka, Beth M. Isaac, Antonine Jean, Noora Majid, Leah Seifu, John Croft, Bindy Crouch, Michelle Macaraig, Allison Lemkin, Guajira Thomas Caceres, Ramona Lall, Cheryl Lawrence, Erica Silverman, Fabienne Laraque, Alyssa Bouscaren, and Jennifer B. Rosen. Varicella outbreak among recent arrivals to new york city, 2022–2024. MMWR. Morbidity and Mortality Weekly Report, 73:478-483, May 2024. URL: https://doi.org/10.15585/mmwr.mm7321a1, doi:10.15585/mmwr.mm7321a1. This article has 2 citations.

  12. (xiran2024preliminaryinvestigationand pages 2-3): Li Xiran, Sun Hongyan, Qin Guixiang, Sun Ying, Li Xiang, Tian Xin, Han Mengying, Wang Ji, and Ji Shangwei. Preliminary investigation and analysis of nucleotide site variability of nine glycoproteins on varicella-zoster virus envelope, jilin province, china, 2010-march 2024. Scientific Reports, Oct 2024. URL: https://doi.org/10.1038/s41598-024-73072-w, doi:10.1038/s41598-024-73072-w. This article has 1 citations and is from a peer-reviewed journal.

  13. (xiran2024preliminaryinvestigationand pages 1-2): Li Xiran, Sun Hongyan, Qin Guixiang, Sun Ying, Li Xiang, Tian Xin, Han Mengying, Wang Ji, and Ji Shangwei. Preliminary investigation and analysis of nucleotide site variability of nine glycoproteins on varicella-zoster virus envelope, jilin province, china, 2010-march 2024. Scientific Reports, Oct 2024. URL: https://doi.org/10.1038/s41598-024-73072-w, doi:10.1038/s41598-024-73072-w. This article has 1 citations and is from a peer-reviewed journal.