Rous sarcoma virus

Rous sarcoma virus
Name	Rous sarcoma virus
Caption	Electron micrograph of Rous sarcoma virus virions
Taxon	Retroviridae
Genus	Alpharetrovirus
Species	Rous sarcoma virus

Rous sarcoma virus. It is a retrovirus that causes sarcoma, a type of connective tissue cancer, in chickens. Its discovery provided the first conclusive evidence that a virus could cause cancer, fundamentally altering the course of cancer research. The study of this agent has been instrumental in identifying oncogenes and understanding the molecular mechanisms of carcinogenesis.

Discovery

The virus was discovered in 1911 by Peyton Rous at the Rockefeller Institute for Medical Research. Rous was investigating a malignant tumor in a Plymouth Rock hen brought to his laboratory. He successfully transmitted the tumor to healthy chickens by injecting a cell-free filtrate, proving the infectious, viral nature of the cancer. This landmark finding was initially met with skepticism, as it challenged prevailing beliefs about cancer etiology. Decades later, the significance of his work was recognized, and Rous was awarded the Nobel Prize in Physiology or Medicine in 1966. Subsequent work by researchers like Howard Temin and David Baltimore on this virus led to the discovery of reverse transcriptase, revolutionizing molecular biology.

Structure

The virion is an enveloped, spherical particle approximately 100 nm in diameter. Its outer lipid bilayer is derived from the host cell membrane and is studded with viral envelope glycoproteins, crucial for binding to host cell receptors. Within the envelope lies a capsid shell that encases the viral genome and associated enzymes. The genome consists of two identical positive-sense single-stranded RNA molecules, making it diploid. Key enzymatic components packaged within the virion include reverse transcriptase, integrase, and protease, all essential for the viral replication cycle. The structural proteins are encoded by the *gag* gene, while the envelope proteins are encoded by the *env* gene.

Replication

Replication follows the characteristic retroviral life cycle. The virus enters a susceptible host cell, typically a fibroblast, via specific receptor-mediated endocytosis. Following uncoating, the viral reverse transcriptase enzyme synthesizes a double-stranded DNA copy of the RNA genome. This viral DNA, known as the provirus, is then transported into the nucleus and integrated into the host cell's chromosomal DNA by the viral integrase. The integrated provirus is transcribed by the host's RNA polymerase II to produce new viral genomic RNA and messenger RNA. These RNA molecules are translated into viral polyproteins, which are subsequently cleaved by the viral protease. New virions assemble at the cell membrane, incorporating the genomic RNA and enzymes, and bud from the cell to acquire their envelope.

Pathogenesis

Infection primarily induces sarcomas at the site of inoculation in chickens, leading to solid, hemorrhagic tumors. The virus exhibits a broad cell tropism but has a particular affinity for connective tissue cells. Infection can be either acute, rapidly producing tumors, or chronic, with a longer latency period. The pathogenic potential is directly linked to the presence of the viral *src* oncogene. While the primary host is avian, certain laboratory-adapted strains can transform mammalian cells in culture, though they typically do not cause tumors in mammalian hosts. The disease progression involves local tumor growth, which can metastasize, ultimately leading to the death of the host.

Oncogenic properties

The transformative capability is due to the *v-src* (viral sarcoma) oncogene, the first oncogene ever discovered. This gene is not required for viral replication but is responsible for the rapid induction of cancer. *V-src* encodes a tyrosine kinase, an enzyme that phosphorylates tyrosine residues on various host cell proteins. This aberrant phosphorylation constitutively activates signaling pathways that control cell growth, division, and survival, leading to uncontrolled proliferation. The cellular counterpart, *c-src*, is a proto-oncogene present in normal chicken and human genomes. The viral version is a mutated, constitutively active form that the virus captured from a host genome during a prior infection, a process known as transduction.

Research and applications

Research on this virus has been foundational in oncology and virology. It provided the first model for studying viral carcinogenesis and led to the oncogene theory of cancer. The discovery of reverse transcriptase by Howard Temin and David Baltimore, using this virus as a key model, earned them the Nobel Prize in Physiology or Medicine in 1975. This enzyme became a crucial tool in molecular biology, enabling the creation of cDNA libraries and the development of techniques like RT-PCR. Studies of its genome facilitated the understanding of retroviral gene regulation and splicing. Furthermore, investigation into its oncogenic mechanisms directly informed the development of targeted cancer therapies, particularly tyrosine kinase inhibitors such as imatinib.

Category:Retroviruses Category:Oncogenic viruses Category:Animal virology