Rous sarcoma virus

Rous sarcoma virus
Virus classification
(unranked):	Virus
Realm:	Riboviria
Kingdom:	Pararnavirae
Phylum:	Artverviricota
Class:	Revtraviricetes
Order:	Ortervirales
Family:	Retroviridae
Genus:	Alpharetrovirus
Species:	Rous sarcoma virus

Rous sarcoma virus (RSV) (/raʊs/) is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in chickens.

As with all retroviruses, it reverse transcribes its RNA genome into

History

RSV was discovered in 1911 by

In 1958, Harry Rubin and Howard Temin developed an assay where chicken embryo fibroblasts could be altered morphologically by RSV infection. Two years later Temin concluded that the transformed morphology of the cells was controlled by a genetic property of RSV. At that time it was unknown, but later the src gene was identified as responsible for morphological transformation in healthy cells. During the 1960s, two findings emerged: replication-competent isolated viruses were related to RSV, but were non-transforming, and an isolated replication-defective strain of RSV was transformation-competent. These two findings gave rise to the notion that viral replication and malignant transformation are separate processes in RSV.^[4]

Rous was awarded the Nobel Prize in Physiology or Medicine for the significance of his discovery in 1966.^[5] Subsequently, other oncogenic human viruses, such as Epstein–Barr virus, were discovered. Furthermore, oncogenes were found initially in retroviruses and then in cells.^[3]

Structure and genome

RSV is a class VI enveloped virus with a positive sense RNA genome having a DNA intermediate.

Freely replicating RSV strains such as Prague-C have four genes:^[6]

• gag
  – encodes capsid proteins
• pol
  – encodes reverse transcriptase
• env – encodes the envelope gene
• src – encodes a tyrosine kinase that attaches phosphate groups to the amino acid tyrosine in host cell proteins.

However, not all RSV strains have all four genes that allow it to both replicate on its own and cause transformation. It is not at all clear whether Rous's original strain was able to replicate on its own or if some descendants acquired this ability later.^[7] Very few acutely oncogenic or transforming retroviruses are capable of replication without a helper virus, making non-defective strains of RSV quite unique.^[8]

The RSV genome has

Src gene

The

The chicken src gene was taken up by RSV and incorporated into its genome.^[10]

The v-Src gene is thought to confer the virus with the advantage of being able to stimulate uncontrolled mitosis of host cells, providing abundant cells for fresh infection.^[11] The src gene is not essential for RSV reproduction but it greatly increases virulence when present.^[9]

Src is a tyrosine kinase involved in regulation of cell growth and differentiation. It has an SH2 and SH3 domain, which are responsible for its activation and deactivation.^[4]

RNA secondary structure

The RNA genome of RSV contains an extremely long

RSV has an envelope which has one glycoprotein: env. Env is made up of gp85 and gp37, which are glycoproteins that assemble into oligomers. The function of env is to bind RSV to the host cell receptor and induce fusion with the target cell in a pH independent manner. The envelope is acquired during exocytosis. The virus buds or pushes on the plasma membrane, which allows it to leave the cell with a new outer membrane from the host cell.^[15][17]

Replication cycle

Cell entry

There are two ways viruses can enter the host cell: cell receptor endocytosis or fusion. Fusion occurs when the virus fuses together with the target cell membrane and releases its genome into the cell. RSV enters the host cell through fusion of the host cell membrane.^[18]

Transcription

In order for the RSV genome transcription to occur, a primer is required. 4S RNA is the primer for RSV and 70S RNA serves as the template for DNA synthesis. Reverse transcriptase, an RNA-dependent