- Viral oncogenesis refers to the process by which certain viruses contribute to the development of cancer.
- Some viruses, known as oncogenic viruses, can cause cancer by directly or indirectly disrupting normal cellular regulation.
Mechanisms
1. Insertion of Viral Oncogenes
- Oncogenes are genes that have the potential to cause cancer when activated. Some viruses carry their own viral oncogenes that can disrupt normal cell function.
- Example: Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia by inserting its oncogenes into host cells and transforming T-cells.
2. Insertional Mutagenesis
- Viruses can integrate their genomes into the host DNA, potentially disrupting critical tumor suppressor genes or activating oncogenes.
- This random insertion of viral DNA into the host genome may lead to mutations that promote uncontrolled cell growth.
- Example: Retroviruses, such as HIV, integrate into the host genome and may activate oncogenes or inactivate tumor suppressor genes, contributing to cancer.
3. Inhibition of Tumor Suppressor Proteins
- Tumor suppressor proteins like p53 and retinoblastoma (Rb) protein normally regulate cell growth and prevent tumor formation.
- Some viruses produce proteins that directly bind and inactivate these tumor suppressors, removing the control on cell division and leading to uncontrolled growth.
- Example: Human papillomavirus (HPV) produces proteins E6 (which targets p53 for degradation) and E7 (which binds and inactivates Rb), leading to cervical cancer and other cancers.
4. Chronic Inflammation and Immune Modulation
- Some viruses induce chronic inflammation, which can lead to tissue damage, increased cell turnover, and mutations over time, increasing the risk of cancer.
- Chronic viral infections also modulate the immune system, allowing infected cells to evade immune surveillance and accumulate mutations.
- Example: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) cause chronic inflammation in the liver, leading to hepatocellular carcinoma.
5. Immortalization of Cells
- Oncogenic viruses can alter cellular pathways to prevent apoptosis (programmed cell death) and promote continuous cell division, leading to the immortalization of cells.
- This process often involves the virus manipulating the host cell cycle, enabling the infected cells to survive longer and accumulate mutations.
- Example: Epstein-Barr virus (EBV) immortalizes B cells, contributing to the development of Burkitt’s lymphoma and other cancers.
6. Indirect Mechanisms: Immunosuppression
- Some viruses weaken the immune system, reducing the body’s ability to detect and destroy abnormal cells, thus promoting cancer development.
- Example: HIV causes immunosuppression by depleting CD4+ T cells, allowing opportunistic infections (like Kaposi’s sarcoma-associated herpesvirus or KSHV) to cause cancer.
7. Latency and Reactivation
- Certain viruses can establish latency, during which they remain dormant in the host cell but may still influence cellular pathways.
- Latent viruses can reactivate and alter the cellular environment, sometimes driving the development of cancer after long periods.
- Example: EBV establishes latency in B cells and can lead to Hodgkin’s lymphoma and nasopharyngeal carcinoma upon reactivation.
8. Epigenetic Changes
- Viruses can alter the epigenetic regulation of host cells by changing the methylation patterns of DNA or modifying histones, leading to the inappropriate expression of oncogenes or the silencing of tumor suppressor genes.
- Example: Merkel cell polyomavirus (MCPyV) can induce epigenetic changes, contributing to Merkel cell carcinoma.
Oncogenic Viruses Associated with Cancer:
- Human papillomavirus (HPV): cervical, anal, and oropharyngeal cancers.
- Epstein-Barr virus (EBV): Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma.
- Hepatitis B and C viruses (HBV and HCV): hepatocellular carcinoma.
- Human T-cell lymphotropic virus type 1 (HTLV-1): adult T-cell leukemia/lymphoma.
- Kaposi’s sarcoma-associated herpesvirus (KSHV): Kaposi’s sarcoma, primary effusion lymphoma.
- Merkel cell polyomavirus (MCPyV): Merkel cell carcinoma.
By disrupting normal cellular control mechanisms, oncogenic viruses drive the accumulation of genetic mutations and uncontrolled cell growth, leading to cancer formation.
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