Rous sarcoma virus (RSV) is an avian retrovirus known for causing sarcomas, a type of connective tissue cancer, in chickens. This virus is a foundational model that revolutionized understanding in virology and cancer research. Its study provided insights into how viruses can induce malignant transformation and laid the groundwork for modern cancer genetics.
The Discovery of a Cancer-Causing Virus
The groundbreaking discovery of a cancer-causing agent occurred in 1911 through the work of American pathologist Peyton Rous. He observed a chicken with a spontaneously arising sarcoma and investigated its cause. Rous successfully transmitted the tumor from the sick chicken to healthy ones by injecting them with a cell-free filtrate derived from the tumor.
This finding was revolutionary; at the time, cancer was widely believed to be non-transmissible and not caused by an infectious agent. The scientific community initially met Rous’s results with skepticism, as the concept of a virus initiating cancer was unprecedented. Despite initial resistance, his persistent research paved the way for a paradigm shift in cancer biology. The profound significance of his discovery was fully recognized decades later when he was awarded the Nobel Prize in Physiology or Medicine in 1966.
How RSV Causes Cancer
Rous sarcoma virus is classified as a retrovirus, characterized by its unique replication strategy. Upon infecting a host cell, the virus delivers its genetic material, RNA, into the cell’s cytoplasm. RSV carries an enzyme called reverse transcriptase.
This enzyme converts the viral RNA genome into a DNA copy, a process “reverse” to the usual flow of genetic information from DNA to RNA. The newly synthesized viral DNA then travels to the cell’s nucleus and integrates into the host cell’s chromosomal DNA. Once integrated, the viral genes become a permanent part of the host cell’s genetic blueprint. These integrated viral genes are then transcribed and translated by the host cell’s machinery, leading to new viral particles and triggering uncontrolled cell growth that culminates in tumor formation.
The First Oncogene
Research on Rous sarcoma virus in the 1970s led to a significant discovery in cancer biology: the identification of the first oncogene. A specific gene carried by RSV, named src, was directly responsible for its cancer-causing ability. This viral version is called v-src.
Investigation uncovered that v-src has a counterpart in normal cells, known as c-src. The cellular c-src gene is a proto-oncogene, regulating cell growth, division, and differentiation. The viral v-src gene is thought to have been acquired from a host cell during an ancient infection. The key difference is that v-src is a mutated or altered version of c-src, causing constant activity. This overrides normal cellular controls and drives uncontrolled cell proliferation, leading to tumor development. This discovery established the principle that cancer can arise from mutations in a cell’s own genes, laying the groundwork for the genetic basis of cancer.
RSV and Human Health
While Rous sarcoma virus effectively induces sarcomas in chickens, it does not cause disease in humans. Despite this, RSV has had a profound impact on human health through its role as a research model. The study of RSV’s retroviral life cycle provided the foundational blueprint for understanding other retroviruses.
This knowledge proved invaluable for scientists investigating human retroviruses, particularly the Human Immunodeficiency Virus (HIV), which causes AIDS. The mechanisms of reverse transcription, integration into the host genome, and viral gene expression, first elucidated with RSV, were directly applicable to understanding HIV’s replication strategy. RSV research also contributed to understanding other human cancer-causing viruses, such as Human T-lymphotropic virus 1 (HTLV-1), associated with a rare form of leukemia.