# HİLAL ÖZYURT 1605A032, Viruses and Cancer

ONCOGENIC VIRUSES

Seven human viruses have been causally associated with the development of certain cancers (Table 9.2).
These viruses directly or indirectly contribute to the development of a cancerous cell, although this is a by-product, rather than a requirement, of infection. It is simply that the growth-promoting properties of the viruses have oncogenic consequences. A common feature of human oncogenic viruses is that they do not initiate productive infection within tumor cells. In fact, some of these viruses become unable to replicate as a result of the changes that occur in the cancerous cell. There are four broad categories of oncogenic viruses: oncogenic retroviruses, RNA tumor viruses, small DNA tumor viruses, and large DNA tumor viruses.


Source: Louten, J. (2016). Influenza Viruses. Essential Human Virology,p.159

**Oncogenic Retroviruses**
Retroviruses are RNA viruses that reverse transcribe their genome into DNA before integrating it into a host cell chromosome.
The first oncogenic viruses discovered, avian leukemia viruses and Rous sarcoma virus (RSV, not to be confused with the human pathogen with the same acronym, respiratory syncytial virus), are retroviruses.
It was later discovered that the retrovirus RSV contains an additional nonessential gene, named src (pronounced “sark”) for its ability to induce sarcomas

Source: Louten, J. (2016). Influenza Viruses. Essential Human Virology,p.160

(A) Shown here is the cDNA following reverse transcription, as evidenced by the two longterminal repeats (LTR) segments that flank the genes. The LTRs are important for integration into the host chromosome. (B) Oncogenic retroviruses encode a viral oncogene that also becomes integrated into the host chromosome. No human retroviruses have been identified that contain oncogenes of cellular origin.

**RNA Tumor Viruses**
In addition to retroviruses, one other human RNA virus has a strong association with oncogenesis: hepatitis C virus (HCV). HCV is an enveloped+ssRNA virus of the family Flaviviridae that infects hepatocytes, the cells of the liver. HCV is also thought to directly contribute to oncogenesis through its effects upon numerous cellular proteins to induce cellular transformation. HCV does not integrate into the host genome. As an RNA virus, the HCV life cycle is entirely cytoplasmic.

Source: Louten, J. (2016). Influenza Viruses. Essential Human Virology,p.162

**Flaviviridae**


Source: https://viralzone.expasy.org/43

Enveloped, spherical, about 50 nm in diameter. The surface proteins are arranged in an icosahedral-like symmetry.


Source: https://viralzone.expasy.org/43

Monopartite, linear, ssRNA(+) genome of about 9.7-12 kb. The genome 3' terminus is not polyadenylated but forms a loop structure. The 5' end has a methylated nucleotide cap (to allow translation) or a genome-linked protein (VPg).
GENE EXPRESSION
The virion RNA is infectious and serves as both the genome and the viral messenger RNA. The whole genome is translated into a polyprotein, which is processed co- and post-translationally by host and viral proteases.

**Small DNA Tumor Viruses**

Three small human DNA viruses are associated with the development of cancers: HBV, MCPyV, and certain types of HPV, known as “high-risk” HPVs.
Although it has many different properties than HCV, HBV shares some similarities with HCV, as well. HBV is a virus that also exhibits tropism for the liver, induces chronic hepatitis and cirrhosis, and causes up to 50% of the cases of HCC.
HBV is an unusual virus. It possesses a partially doublestranded 3.2 kb DNA genome and is one of the few nonretroviruses to encode and utilize a reverse transcriptase to complete its life cycle.

Papillomaviruses are small, nonenveloped icosahedral viruses (Fig.A) with circular dsDNA genomes that infect the basal layer of cells in the skin or mucosal epithelium and cause papillomas or wartlike growths. Low-risk HPVs, such as types 6 and 11, cause genital warts (Fig.B), but high-risk HPVs, including types 16 and 18, act as carcinogens and are detected in 99% of cervical cancers.

Source: Louten, J. (2016). Influenza Viruses. Essential Human Virology,p.164

**Large DNA Tumor Viruses**

A hallmark of all herpesviruses is that they are never fully cleared from the host, establishing latency within cells after the initial infection.
EBV and KSHV are two viruses that are associated with the development of tumors in humans. As herpesviruses, EBV and KSHV are large, enveloped viruses with complex dsDNA genomes that each encodes over 50 genes.

Source: Louten, J. (2016). Influenza Viruses. Essential Human Virology,p.165

EBV, which infects B lymphocytes and epithelial cells, causes 90% of the cases of infectious mononucleosis, or “mono.” Additionally, the virus also plays a role in the development of B cell lymphomas, malignancies that arise in the lymph nodes or in lymphatic tissues. These include Burkitt’s lymphoma (Fig. A and B) and Hodgkin’s lymphoma, as well as non-Hodgkin’s lymphoma in immunodeficient individuals.