Oncogenic Viruses

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Oncogenic Viruses - Tiny Tumour Triggers

  • Definition: Viruses causing cancer by disrupting host cell cycle control and growth regulation.
  • Classification:
    • DNA Viruses: e.g., HPV, EBV, HBV, HHV-8, MCPyV.
    • RNA Viruses: e.g., HTLV-1, HCV.
  • General Mechanisms:
    • Direct: Viral oncogenes (v-onc) integrate or persist episomally. Key actions: activate proto-oncogenes, inactivate tumour suppressor genes (TSGs) like p53, Rb. Results in cell transformation, immortalization.
    • Indirect: Chronic inflammation (e.g., HBV, HCV leading to hepatocellular carcinoma) or immunosuppression.
  • Key Terms: Proto-oncogenes, TSGs (p53, Rb), transformation, immortalization, latency (viral persistence).

⭐ HPV E6 oncoprotein targets p53 for ubiquitin-mediated degradation; E7 oncoprotein binds and inactivates Rb.

Oncovirus-induced tumorigenesis

DNA Oncogenic Viruses - Genome Invaders

These viruses integrate their genetic material or viral proteins to disrupt host cell cycle regulation, leading to uncontrolled proliferation.

  • Key Mechanisms:
    • Inactivation of tumor suppressor proteins (p53, Rb)
    • Activation of proto-oncogenes
    • Chronic inflammation leading to cell damage and regeneration

Mechanisms of Oncogenic Viral Infection Leading to Cancer

VirusFamilyKey Proteins/GenesTarget Pathways/MechanismAssociated Cancers
HPVPapillomaviridaeE6, E7E6 → p53 degradation; E7 → Rb inactivationCervical, anogenital, oropharyngeal carcinomas 📌 16, 18 >70% cervical Ca
EBVHerpesviridaeLMP1, EBNA2LMP1 (CD40 mimic), EBNA2 (gene activation)Burkitt's & Hodgkin's lymphoma, Nasopharyngeal Ca, Gastric Ca
HBVHepadnaviridaeHBxHBx → cell cycle disruption, p53 inactivation (indirect)Hepatocellular carcinoma (HCC)
HHV-8 (KSHV)HerpesviridaeLANA, v-cyclin, v-FLIPProliferation ↑, Apoptosis ↓Kaposi's sarcoma, Primary effusion lymphoma
MCVPolyomaviridaeLT & sT antigensLT → p53 & Rb inactivationMerkel cell carcinoma

RNA Oncogenic Viruses - Reverse Rebels

RNA viruses with oncogenic potential, primarily HTLV-1 (a retrovirus) and HCV (a Flavivirus). They employ distinct mechanisms for carcinogenesis.

  • Human T-cell Lymphotropic Virus 1 (HTLV-1)
    • Retrovirus; integrates into host genome.
    • Key protein: Tax (transcriptional activator/co-activator).
    • Mechanism: Tax transactivates cellular genes (e.g., IL-2, IL-2R), promotes cell proliferation, induces genomic instability, inhibits apoptosis.
    • Cancer: Adult T-cell Leukemia/Lymphoma (ATLL).
  • Hepatitis C Virus (HCV)
    • Flavivirus; RNA virus, does not integrate into host DNA.
    • Key proteins: Core, NS3, NS5A.
    • Mechanism: Chronic inflammation & regeneration → cirrhosis; oxidative stress → DNA damage; viral proteins directly alter cell signaling pathways (e.g., interfere with p53).
    • Cancer: Hepatocellular Carcinoma (HCC).
VirusFamilyKey ProteinsMechanismAssociated Cancers
HTLV-1RetroviridaeTaxTransactivation of cellular genes, genomic instability, anti-apoptosisATLL
HCVFlaviviridaeCore, NS3, NS5AChronic inflammation, oxidative stress, direct protein effects on signalingHCC

HTLV-1 Tax protein interaction and disease

📌 RNA Rebels: HTLV-1 Tax Activates T-cells; HCV Causes Hepatocellular Carcinoma via Chronic inflammation.

High‑Yield Points - ⚡ Biggest Takeaways

  • HPV types 16, 18 are key for cervical cancer; E6 targets p53, E7 targets Rb.
  • EBV is associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's lymphoma.
  • HBV & HCV significantly increase risk for hepatocellular carcinoma (HCC).
  • HTLV-1 is the causative agent for Adult T-cell Leukemia/Lymphoma (ATLL).
  • KSHV/HHV-8 causes Kaposi's sarcoma and primary effusion lymphoma.
  • Key mechanisms: inactivating tumor suppressors (p53, Rb), activating oncogenes, viral integration, chronic inflammation.

Practice Questions: Oncogenic Viruses

Test your understanding with these related questions

Which of the following is NOT typically associated with chronic HPV infection?

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Flashcards: Oncogenic Viruses

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Which virus is a risk factor for basal cell carcinoma?_____

TAP TO REVEAL ANSWER

Which virus is a risk factor for basal cell carcinoma?_____

Human Papilloma Virus

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