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Oncogenic DNA viruses and their mechanisms of oncogenesis

Oncogenic DNA viruses are viruses that have the ability to cause cancer in their host cells. These viruses can integrate their genetic material into the host cell’s DNA, disrupt normal cellular functions, and promote uncontrolled cell growth, leading to the development of cancer.

  1. Human Papillomavirus (HPV):
    • Type of Cancer: HPV is strongly associated with cervical cancer and is also implicated in other cancers such as anal, penile, and oropharyngeal cancers.
    • Mechanism of Oncogenesis: HPV primarily infects epithelial cells and expresses viral oncoproteins, E6 and E7. E6 targets the tumor suppressor protein p53 for degradation, while E7 targets the retinoblastoma (Rb) protein, leading to the disruption of cell cycle control and apoptosis.
  2. Epstein-Barr Virus (EBV):
    • Type of Cancer: EBV is linked to several cancers, including Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, and gastric carcinoma.
    • Mechanism of Oncogenesis: EBV infects B cells and epithelial cells. It can establish latency in B cells and express latent proteins such as LMP1 and EBNA2, which can promote cell proliferation and inhibit apoptosis. LMP1, in particular, mimics a constitutively active CD40 receptor, activating various signaling pathways.
  3. Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV):
    • Type of Cancer: Chronic infection with HBV or HCV is a major risk factor for the development of hepatocellular carcinoma (liver cancer).
    • Mechanism of Oncogenesis: Both HBV and HCV can cause chronic inflammation in the liver, leading to cirrhosis, and subsequently, hepatocellular carcinoma. Specific viral proteins, such as HBx in HBV and core, NS3, and NS5A in HCV, play roles in disrupting cellular processes, promoting cell survival, and interfering with tumor suppressors.
  4. Human Herpesvirus 8 (HHV-8):
    • Type of Cancer: HHV-8 is associated with Kaposi’s sarcoma, especially in immunocompromised individuals.
    • Mechanism of Oncogenesis: HHV-8 encodes several proteins that can promote cell survival and proliferation. The viral protein vFLIP, for example, mimics cellular FLICE inhibitory protein (c-FLIP) and inhibits apoptosis, contributing to the development of Kaposi’s sarcoma.
  5. Merkel Cell Polyomavirus (MCPyV):
      • The exact mechanisms are not fully understood, but MCPyV is associated with Merkel cell carcinoma. Viral DNA integration and expression of viral oncoproteins may contribute to cellular transformation.

6. Adenoviruses:

  • Certain adenovirus types have been linked to cancers, especially in immunocompromised individuals. Mechanisms include viral DNA integration and disruption of cellular pathways regulating cell cycle and apoptosis.

 

Oncogenic RNA viruses and their mechanisms of oncogenesis

Oncogenic RNA viruses are viruses that can cause cancer by infecting host cells and altering their normal cellular functions. These viruses typically carry RNA as their genetic material and have specific mechanisms that contribute to oncogenesis.

  1. Human T-cell Lymphotropic Virus Type 1 (HTLV-1):
    • Type of Cancer: HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATLL) and can also cause a neurological disorder known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
    • Mechanism of Oncogenesis: HTLV-1 encodes a viral oncoprotein called Tax, which plays a crucial role in cellular transformation. Tax activates various cellular signaling pathways, including those involving NF-κB and CREB, leading to increased cell proliferation and resistance to apoptosis.
  2. Hepatitis C Virus (HCV):
    • Type of Cancer: Chronic HCV infection is a significant risk factor for the development of hepatocellular carcinoma (liver cancer).
    • Mechanism of Oncogenesis: Similar to hepatitis B virus (HBV), HCV can cause chronic inflammation in the liver, leading to cirrhosis and eventually hepatocellular carcinoma. HCV core and NS5A proteins have been implicated in promoting cell survival, inhibiting apoptosis, and contributing to liver cancer development.
  3. Human Immunodeficiency Virus (HIV):
    • Type of Cancer: While HIV itself does not directly cause cancer, individuals infected with HIV have an increased risk of developing certain cancers, such as Kaposi’s sarcoma, non-Hodgkin lymphoma, and invasive cervical cancer.
    • Mechanism of Oncogenesis: HIV weakens the immune system, making individuals more susceptible to infections with oncogenic viruses like human herpesvirus 8 (HHV-8) and Epstein-Barr virus (EBV). Additionally, chronic immune activation and inflammation associated with HIV infection contribute to the development of AIDS-related cancers.
  4. Retroviruses (e.g., Murine Leukemia Virus – MLV):
    • Type of Cancer: MLV is a retrovirus that can cause leukemia and lymphoma in mice.
    • Mechanism of Oncogenesis: Retroviruses integrate their viral DNA into the host genome, and in the case of MLV, this integration can lead to the activation of cellular oncogenes or the disruption of tumor suppressor genes. The viral oncogene v-myc is an example of a gene carried by some retroviruses that can contribute to cellular transformation.