Oncogenic RNA Viruses Introduction Oncogenic RNA viruses are a class of viruses whose genetic material (RNA) can induce cancer. Unlike DNA viruses, which integrate into the host genome and directly influence cellular mechanisms, RNA viruses can cause cancer through a range of indirect mechanisms, including chronic inflammation, alteration of host cell signaling, and the introduction of viral oncogenes. Understanding these viruses is crucial for developing strategies to prevent and treat virus-induced cancers. 1. Overview of Oncogenic RNA Viruses Definition and Characteristics   Oncogenic RNA Viruses: RNA viruses that have the potential to cause cancer in humans and animals. Mechanisms of Oncogenesis: These viruses can induce cancer through: o Insertional Mutagenesis: Integration of viral RNA or proviral DNA into the host genome. o o Chronic Inflammation: Long-term viral infections leading to persistent inflammation that can drive cancer development. Viral Oncogenes: Expression of viral genes that interfere with cellular regulatory mechanisms. Types of Oncogenic RNA Viruses 1. Retroviruses 2. Hepadnaviruses 3. HIV (Human Immunodeficiency Virus) 2. Retroviruses Definition Retroviruses are RNA viruses that reverse-transcribe their RNA into DNA, which then integrates into the host genome. Some retroviruses are oncogenic and can cause cancer through the activation of proto-oncogenes or the disruption of tumor suppressor genes. Key Examples  Human T-cell Leukemia Virus Type 1 (HTLV-1) o o  Disease: Adult T-cell Leukemia/Lymphoma (ATLL) Mechanism: HTLV-1 encodes the Tax protein, which promotes cellular proliferation and inhibits apoptosis. Tax activates cellular signaling pathways like NF-κB and AP-1, leading to the transformation of T-cells. Rous Sarcoma Virus (RSV) o o Disease: Sarcoma in chickens. Mechanism: RSV carries the v-SRC oncogene, which is a mutated version of the cellular SRC proto-oncogene. The v-SRC protein is a constitutively active tyrosine kinase that promotes uncontrolled cell growth and transformation. Mechanisms of Oncogenesis   Insertional Mutagenesis: Viral integration disrupts normal cellular genes. Expression of Oncogenes: Viral proteins promote cell proliferation and survival. 3. Hepadnaviruses Definition Hepadnaviruses are DNA viruses that replicate through an RNA intermediate but can also be considered RNA viruses due to their replication cycle involving an RNA phase. Key Examples  Hepatitis B Virus (HBV) o Disease: Hepatocellular Carcinoma (HCC) o Mechanism: HBV causes chronic hepatitis and liver inflammation, which can lead to cirrhosis and increase the risk of liver cancer. HBV produces HBx protein, which can promote carcinogenesis by interfering with cellular signaling pathways, including the inhibition of p53 and activation of NF-κB. Mechanisms of Oncogenesis   Chronic Inflammation: Persistent viral infection leads to liver damage and regeneration, which can promote cancer development. Viral Oncogene: HBx protein contributes to liver carcinogenesis through multiple mechanisms including the activation of cellular proto-oncogenes and the inhibition of tumor suppressor pathways. 4. Human Immunodeficiency Virus (HIV) Definition HIV is a retrovirus that causes AIDS. While HIV itself is not directly oncogenic, it can lead to an increased risk of various cancers due to immunosuppression. Key Examples   Associated Cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, Invasive Cervical Cancer. Mechanism: HIV-induced immunosuppression leads to opportunistic infections and the development of cancers associated with other oncogenic viruses, such as HHV-8 (Kaposi’s Sarcoma-associated Herpesvirus) and HPV (Human Papillomavirus). Mechanisms of Oncogenesis  Immunosuppression: HIV depletes CD4+ T cells, weakening the immune system and allowing oncogenic viruses to persist and cause cancer. 5. Prevention and Treatment Prevention Strategies  Vaccination: Vaccines are available for some oncogenic RNA viruses. o o HBV Vaccine: Effective in preventing HBV infection and associated liver cancer. HPV Vaccine: Prevents infections by oncogenic HPV types, reducing the risk of cervical and other cancers.  Antiviral Therapies: Drugs that target viral replication can reduce the risk of cancer in chronic viral infections. o o Antiretrovirals: Used to manage HIV and prevent AIDS-related cancers. HBV Treatments: Antivirals like tenofovir and entecavir help manage chronic HBV infection. Therapeutic Approaches   Targeted Therapies: New treatments aim at specific viral proteins or host cell targets to inhibit cancer progression. Immunotherapies: Emerging therapies focus on stimulating the immune system to target cancer cells or the viruses that cause them.