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
Show evidence (2 references)
"Viruses are the causative agents of 10%-15% of human cancers worldwide."
Establishes viral infection as the etiologic trigger for a substantial fraction of human cancers. Evidence source is OTHER because this is a review.
"Typically, cancer develops years to decades following the initial infection."
Supports the long latency between persistent infection and malignant transformation that characterizes viral oncogenesis.
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
Show evidence (2 references)
"integration of viral DNA into the human genome can also play an important role in promoting tumor development for"
Supports viral genome integration as a contributor to tumor development for several oncogenic viruses.
"This process often targets fragile sites in the human genome, causing structural rearrangements that disrupt genes, activate proto-oncogenes, and increase genomic instability, all contributing to tumorigenesis."
Details how incidental oncovirus integration disrupts host genes, activates proto-oncogenes, and drives genomic instability.
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
Show evidence (2 references)
"the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB."
Directly supports the conserved mechanism of viral oncoprotein-mediated inactivation of the p53 and RB tumor-suppressor axes.
"The E6 protein causes degradation of p53 leading to impaired cellular stress response. In contrast, the E7 protein impairs the activity of retinoblastoma protein (pRb) resulting in continuous cell cycle propagation."
Provides the worked HPV archetype (E6-p53, E7-RB) of the conserved tumor-suppressor-inactivation node. Evidence source is OTHER because this is a review article.
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.
Show evidence (1 reference)
"The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage."
Establishes genomic instability as the dominant consequence of viral oncogenic reprogramming.