This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "viral_oncogenesis#Host Tumor Suppressor Inactivation and Signaling Hijack"). The module defines the expected pathophysiology structure; conforming nodes in disorder files should include the corresponding biological processes and causal edges, specialized to their virus/tumor context. Key virus-specific substitutions: HPV E6/E7 (p53/RB); EBV LMP1/EBNA; HBV HBx; HTLV-1 Tax/HBZ; Merkel cell polyomavirus large T antigen; KSHV LANA/vCyclin/vFLIP. The chronic-inflammation route to viral cancer (e.g. HBV/HCV-driven hepatocellular carcinoma) is modeled separately in tumor_promoting_inflammation, and the adaptive immune-evasion arm in immune_checkpoint_blockade. Key conformance target: "viral_oncogenesis#Host Tumor Suppressor Inactivation and Signaling Hijack".
Persistent Oncogenic Virus Infection
trigger
Long-term persistence of an oncogenic virus establishes a reservoir of infected cells and is the necessary first step of viral carcinogenesis. Only a minority of persistently infected individuals ever progress to cancer, and malignancy typically emerges years to decades after the initial infection. Substitutions include high-risk HPV, Epstein-Barr virus, hepatitis B/C virus, HTLV-1, Merkel cell polyomavirus, and Kaposi sarcoma-associated herpesvirus.
Downstream
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Viral Oncoprotein Expression and Genome Integration
Viral Oncoprotein Expression and Genome Integration
central effector
Deregulated expression of the virus's oncoproteins is the molecular engine of transformation. For several DNA tumor viruses (HPV, HBV, Merkel cell polyomavirus) this is frequently accompanied by incidental integration of viral DNA into the host genome; integration is not required for viral replication but, by targeting fragile sites and disrupting both viral gene regulation and host loci, it stabilizes oncoprotein expression, activates proto-oncogenes, and seeds genomic instability. Conforming entries substitute the virus-specific oncoprotein (e.g., HPV E6/E7 driven by loss of E2 repression on integration).
Downstream
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Host Tumor Suppressor Inactivation and Signaling Hijack
Host Tumor Suppressor Inactivation and Signaling Hijack
central effector
The conserved central node of the module: virus-encoded oncoproteins inactivate the core host tumor-suppressor axes - p53 and the RB/p16-CDK cell-cycle brake - and constitutively activate host proliferative and survival signaling. The archetype is high-risk HPV, whose E6 drives p53 degradation and whose E7 inactivates RB to force G1/S transit; EBV LMP1 mimics constitutive CD40/NF-kB signaling, HBx perturbs p53, HTLV-1 Tax activates NF-kB, and Merkel cell polyomavirus large T antigen binds RB. The net effect is override of cell-cycle checkpoints and apoptosis in the infected cell.
Used by disorders
Hodgkin Lymphoma
as EBV LMP1-Mediated NF-kappaB Activation (EBV-positive Classic HL)
Downstream
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Genomic Instability and Deregulated Proliferation
Genomic Instability and Deregulated Proliferation
consequence
Loss of p53/RB control, together with virus-induced replication stress and integration-associated DNA breakage, produces chromosomal instability and an accumulation of mutations and DNA damage in the infected clone. This mutator state - often combined with virally driven replicative immortality (e.g. HPV E6-induced hTERT/telomerase reactivation) - permits progressive clonal evolution toward malignancy.