20.21: Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.

RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open reading frames or ORFs - Gag, Pol, Env, and Src. The first three genes (gag, pol, and env) encode various structural components and enzymes that are required to generate a functional retrovirus within the host cell. In contrast, viral Src is the viral counterpart to the cellular proto-oncogene c-Src and encodes a protein tyrosine kinase.

Upon infection into a host cell, the viral genome is reverse transcribed into proviral DNA. The proviral DNA then integrates into the host genome and uses host cell machinery to get transcribed into RNA. This helps to mask the viral RNA and make it resemble a cellular mRNA. Translation of this RNA in the host cell produces all viral proteins essential for its replication along with the viral Src protein. The viral Src protein is an oncogene that leads to abnormal cell growth and proliferation when expressed inside the host cell.

Retroviruses are a group of single-stranded RNA viruses with the ability to integrate their genome into the host cell DNA.

For example, the Rous sarcoma virus or RSV causes cancer in chickens. Its viral genome contains an oncogene, viral-Src, or v-Src, which is a homolog of the cellular-Src or c-Src. c-Src itself is a proto-oncogene, as it is important for normal vertebrate cell growth.

The v-Src oncogene, when expressed inside the host cell, produces a mutated protein that is hyperactive and leads to abnormal cell growth and cancer progression.

However, the v-Src gene is irrelevant to the survival or replication of the virus. The virus likely acquired it accidentally from another host cell in the past, and the gene subsequently acquired mutations that transformed it into an oncogene.