9.21
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. H…
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.
View the full transcript and gain access to JoVE Core videos
Q1: What is Rous sarcoma virus and how does it cause cancer?
Rous sarcoma virus (RSV) is a retrovirus discovered in 1911 that causes tumors in chickens. RSV integrates its RNA genome into host cell DNA and carries the viral Src oncogene, which produces a hyperactive mutated protein. When expressed in host cells, this protein drives abnormal cell growth and cancer progression, making RSV a cancer-causing infectious agent.
Q2: How does RSV's genome structure differ from other retroviruses?
RSV contains two copies of plus-strand RNA with four main open reading frames: Gag, Pol, Env, and Src. The first three genes encode structural components and enzymes needed for viral replication. The Src gene is unique to RSV and encodes a protein tyrosine kinase that functions as an oncogene, distinguishing it from standard retroviral genomes.
Q3: What is the relationship between viral Src and cellular Src?
Viral Src (v-Src) is a mutated homolog of the cellular proto-oncogene c-Src. While c-Src is essential for normal vertebrate cell growth, v-Src becomes hyperactive and oncogenic when expressed in host cells. RSV likely acquired the c-Src gene accidentally from a host cell in the past, and subsequent mutations transformed it into a cancer-causing oncogene.
Q4: How does RSV integrate into the host cell genome?
Upon infection, RSV's RNA genome is reverse transcribed into proviral DNA. This proviral DNA then integrates into the host genome and is transcribed into RNA using host cell machinery. The viral RNA is masked to resemble cellular mRNA, allowing host ribosomes to translate it and produce all viral proteins, including the oncogenic Src protein.
Q5: Why is the Src gene not essential for RSV replication?
The v-Src gene is irrelevant to RSV survival or replication. The virus carries it as an accidental acquisition from a past host cell that subsequently acquired mutations. While v-Src drives cancer in infected cells, it is not required for the virus to replicate or spread, making it a passenger oncogene rather than a core viral component.
Q6: What historical significance does RSV have in cancer research?
F. Peyton Rous discovered RSV in 1911 as a filterable transmissible agent causing tumors in chickens, earning him the Nobel Prize in 1966. His experiments demonstrated that infectious agents could cause cancer, leading to the discovery of many cancer-causing viruses in animals and humans and establishing the viral etiology of certain cancers.
Q7: How does RSV infection lead to abnormal cell growth?
RSV's viral Src protein is a hyperactive protein tyrosine kinase that disrupts normal cellular signaling when expressed in host cells. This hyperactivity triggers abnormal cell proliferation and growth, ultimately leading to cancer progression. The mechanisms of retrovirus-induced cancers involve this oncogenic protein overriding normal cell growth controls.