Basic Introduction to oncogenic viruses

Define oncogenic viruses.

Viruses that can cause or contribute to the development of cancer by altering cellular growth control mechanisms.

Who discovered the first oncogenic virus and when?

Peyton Rous in 1911 discovered a filterable agent causing tumors in chickens—later identified as an acutely transforming retrovirus (Rous sarcoma virus).

What percentage of human cancers are caused by viruses?

Approximately 15–20% of human cancers worldwide.

List examples of DNA oncogenic viruses.

EBV (Epstein–Barr Virus), HPV (Human Papillomavirus), HBV (Hepatitis B Virus), and KSHV (Kaposi’s Sarcoma–associated Herpesvirus).

List examples of RNA oncogenic viruses.

HCV (Hepatitis C Virus) and HTLV-1 (Human T-cell Leukemia Virus Type 1).

Name cancers linked to viral infections.

Cervical carcinoma, hepatocellular carcinoma, Burkitt’s lymphoma, Kaposi’s sarcoma, adult T-cell leukemia.

Why is viral infection alone insufficient to cause cancer?

Oncogenesis is multifactorial and requires additional factors such as genetic mutations, immunosuppression, and chronic inflammation.

Define oncogene.

A gene whose dysregulation promotes malignant transformation.

Define proto-oncogene.

A normal cellular gene that can become an oncogene when mutated or overexpressed.

Define tumor suppressor gene.

A gene (e.g., p53, Rb) that restrains cell cycle progression and promotes apoptosis.

Define viral integration.

Insertion of viral DNA into the host genome, which can alter expression of nearby cellular genes.

Define transformation (in the oncogenic sense).

Stable, heritable changes that convert a normal cell into a neoplastic one.

Define latency.

Persistence of the viral genome in host cells with limited gene expression.

Define transactivation.

Viral proteins upregulate transcription of viral or cellular genes.

What are the three general mechanisms by which viruses cause cancer?

(1) Integration into host DNA, (2) Expression of viral oncogenes altering signaling, (3) Chronic inflammation and cell regeneration.

Explain why cancer is a multi-step process.

Cancer results from a combination of gain-of-function mutations in proto-oncogenes and loss-of-function mutations in tumor suppressor genes.

What is a common feature of human viral oncogenesis?

Oncoviruses are necessary but not sufficient for cancer; cancer develops years after infection, often under chronic or immunosuppressed conditions.

Name three cofactors that contribute to viral oncogenesis.

Immunosuppression, chronic inflammation, environmental mutagens.

What are the criteria for classifying a virus as a tumor virus?

(1) Viral genome present in tumor cells, (2) Viral infection transforms cells in vitro, (3) Viral genes identified that transform cells, (4) Animal infection induces tumors.

Why can’t human oncoviruses be tested in animal models?

Human-specific viral tropism prevents full replication or transformation in non-human hosts.

What proportion of human cancers is caused by HPV?

About 5% of all human cancers worldwide.

Which HPV genotypes are most oncogenic?

HPV-16 and HPV-18.

Which two HPV proteins are key to oncogenesis and what do they target?

E6 targets p53 for degradation; E7 targets Rb tumor suppressor for degradation.

Why is HPV integration important for cervical cancer?

Integration disrupts viral replication genes, leading to persistent expression of oncogenes E6 and E7.

Which virus is the major cause of hepatocellular carcinoma (HCC)?

Hepatitis B virus (HBV).

What family does HBV belong to?

Hepadnaviridae.

How does HBV contribute to cancer?

By integrating into host DNA (often disrupting p53) and causing chronic liver inflammation and regeneration.

What is the size and type of the HBV genome?

Small, 3.5 kb circular partially double-stranded DNA.

What virus is associated with Burkitt’s lymphoma and nasopharyngeal carcinoma?

Epstein–Barr Virus (EBV).

Which EBV protein is essential for oncogenesis?

LMP-1 (Latent Membrane Protein 1).

Why do most EBV infections not lead to cancer?

Because additional cofactors like malaria and c-myc translocation (8:14) are required for malignant transformation.

What type of virus is KSHV/HHV-8?

A large double-stranded DNA virus of the herpesviridae family.

What cancers are associated with KSHV infection?

Kaposi’s sarcoma and body cavity B-cell lymphomas (especially in AIDS patients).

Which viral family does HCV belong to?

Flaviviridae.

Why can’t HCV cause cancer by integration?

Because it is an RNA virus and does not integrate into host DNA.

How does HCV promote hepatocellular carcinoma?

Through chronic inflammation, liver cell regeneration, and expression of viral proteins that alter host gene expression.

What type of viruses are retroviruses?

Enveloped RNA viruses that replicate through reverse transcription and integration into host DNA.

Give an example of a retrovirus oncogene.

v-src from Rous sarcoma virus (RSV), responsible for causing sarcoma in chickens.

What are the four main mechanisms of retrovirus-induced cell transformation?

(1) Transduction of oncogenes, (2) Insertional activation of proto-oncogenes, (3) Insertional inactivation of tumor suppressor genes, (4) Transformation by viral transactivator proteins (e.g., HTLV tax gene).

Explain insertional activation.

Retroviral integration near a proto-oncogene activates it via viral promoters or enhancers.

Explain insertional inactivation.

Retroviral integration within a tumor suppressor gene disrupts its function.

Describe the SCID gene therapy complication.

Retroviral vectors inserted near proto-oncogene LMO2, causing T-cell leukemia in treated patients.

How can virus-induced cancers be prevented?

Through immunization (HBV, HPV vaccines) and antiviral therapies to prevent chronic infections.

What are the major successes in viral cancer prevention?

HBV vaccine (prevents hepatocellular carcinoma) and HPV vaccine (prevents cervical cancer and genital warts).

Why are virus-induced cancers challenging to treat?

Limited animal models and complexity of virus-host interactions hinder preclinical testing.