Rous sarcoma virus

Rous sarcoma virus (RSV) (/raʊs/) is a retrovirus and is the

first oncovirus to have been described. It causes sarcoma in Rous sarcoma virus
chickens. Virus classification
As with all retroviruses, it reverse transcribes its RNA genome (unranked): Virus
into cDNA before integration into the host DNA. Realm: Riboviria
Kingdom: Pararnavirae

Contents Phylum: Artverviricota

History Class: Revtraviricetes

Structure and genome Order: Ortervirales

Src gene Family: Retroviridae
RNA secondary structure
Genus: Alpharetrovirus
Gag protein
RSV envelope Species: Rous sarcoma
virus
Replication cycle
Cell entry
Transcription
References
External links

History
RSV was discovered in 1911 by Peyton Rous, working at Rockefeller University in New York City, by
injecting cell free extract of chicken tumour into healthy Plymouth Rock chickens. The extract was found
to induce oncogenesis. The tumour was found to be composed of connective tissue (a sarcoma).[1][2] Thus,
RSV became known as the first oncogenic retrovirus that could be used to study the development of cancer
molecularly.[3]

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 Retroviral 3'UTR stability
genome having a DNA intermediate. element
RSV has four genes:

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.

The RSV genome has terminal repeats enabling its integration into
the host genome and also overexpression of RSV genes.

Src gene Predicted secondary structure of

the Rous sarcoma virus retroviral
The src gene is oncogenic as it triggers uncontrolled growth in 3'UTR stability element
abnormal host cells. It was the first retroviral oncogene to be Identifiers
discovered.[6] It is an acquired gene, found to be present
Rfam RF01417 (http://rf
throughout the animal kingdom with high levels of conservation
am.org/family/RF
between species.
01417)
The src gene was taken up by RSV and incorporated into its Other data
genome conferring it with the advantage of being able to stimulate
RNA type Cis-reg
uncontrolled mitosis of host cells, providing abundant cells for
fresh infection. PDB structures PDBe (http://www.
ebi.ac.uk/pdbe/en
The src gene is not essential for RSV proliferation but it greatly try/search/index/?
increases virulence when present. searchParams=%
7B%22rfam_acce
Src is a tyrosine kinase involved in regulation of cell growth and
differentiation. It has an SH2 and SH3 domain, which are ssion%22:%5B%7
responsible for its activation and deactivation.[4] B%22value%22:%
22RF01417%2
2,%22condition
RNA secondary structure 1%22:%22AND%
22,%22condition
The RNA genome of RSV contains an extremely long 3' UTR
2%22:%22Equa
that ranges between 5–7 kb in length which would usually direct it
l%20to%22%7D%
toward nonsense mediated decay (NMD) within the eukaryotic
host cell. A conserved secondary structure element has been 5D,%22resultStat
identified within the 3'UTR and is known as the Rous Sarcoma e%22:%7B%22ta
Virus Stability Element (RSE).[7] This element has been shown to bIndex%22:0,%22
prevent the degradation of the unspliced viral RNA.[7] paginationIndex%
22:1,%22perPag
The RSE element was first identified in the genome of the Rous e%22:%2210%2
Sarcoma Virus but appears to be widely conserved across the 2,%22sortBy%2
avian retrovirus family. The RSE element is ~300 bp in length and 2:%22release_dat
located downstream of the gag natural translational termination
codon. The secondary structure of the RSE element has been e%20desc%22%7
determined by RNAse digestion and SHAPE chemistry D%7D)
analysis.[8]

Other elements that have been identified in RSV include a primer binding site.[9]

Gag protein

Gag proteins are necessary for virion assembly and mature virus infection of the host cell. The gag protein
(Pr76) for RSV contains 701 amino acids. It is cleaved by virus encoded protease, releasing products found
in the infectious virion. These cleaved products include the matrix (MA), capsid (CA), and nucleocapsid
(NC), which are able to enter other pathways to infect new cells.[10][11]

RSV envelope

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.[10][12]

Replication cycle

Cell entry

There are two ways viruses can enter the host cell: cell receptor endocytosis or fusion. Endocytosis is the
process where the virus binds a receptor on the target cell membrane, and the virus is taken into or
endocytosed into the cell. Endocytosis can either be pH independent or pH dependent. 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.[13]

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 DNA
polymerase, transcribes viral RNA into the full length DNA complement.[14]

References
1. Rous P (September 1910). "A Transmissible Avian Neoplasm (Sarcoma of the Common
Fowl)" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2124810). J. Exp. Med. 12 (5): 696–
705. doi:10.1084/jem.12.5.696 (https://doi.org/10.1084%2Fjem.12.5.696). PMC 2124810 (htt
ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2124810). PMID 19867354 (https://pubmed.ncb
i.nlm.nih.gov/19867354).
 2. Rous P (April 1911). "A Sarcoma of the Fowl Transmissible by an Agent Separable from the
Tumor Cells" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2124874). J. Exp. Med. 13 (4):
397–411. doi:10.1084/jem.13.4.397 (https://doi.org/10.1084%2Fjem.13.4.397).
PMC 2124874 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2124874). PMID 19867421
(https://pubmed.ncbi.nlm.nih.gov/19867421).
3. Weiss RA, Vogt PK (November 2011). "100 years of Rous sarcoma virus" (https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC3256973). J. Exp. Med. 208 (12): 2351–5.
doi:10.1084/jem.20112160 (https://doi.org/10.1084%2Fjem.20112160). PMC 3256973 (http
s://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256973). PMID 22110182 (https://pubmed.ncbi.
nlm.nih.gov/22110182).
4. Martin GS (June 2001). "The hunting of the Src". Nat. Rev. Mol. Cell Biol. 2 (6): 467–75.
doi:10.1038/35073094 (https://doi.org/10.1038%2F35073094). PMID 11389470 (https://pub
med.ncbi.nlm.nih.gov/11389470). S2CID 205016442 (https://api.semanticscholar.org/Corpu
sID:205016442).
5. Nobelprize.org The Nobel Prize in Physiology or Medicine 1966: Peyton Rous (https://www.
nobelprize.org/nobel_prizes/medicine/laureates/1966/rous.html), retrieved 1 Jul 2012
6. Vogt PK (September 2012). "Retroviral oncogenes: a historical primer" (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC3428493). Nat. Rev. Cancer. 12 (9): 639–48.
doi:10.1038/nrc3320 (https://doi.org/10.1038%2Fnrc3320). PMC 3428493 (https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC3428493). PMID 22898541 (https://pubmed.ncbi.nlm.nih.gov/2
2898541).
7. Weil JE, Beemon KL (January 2006). "A 3' UTR sequence stabilizes termination codons in
the unspliced RNA of Rous sarcoma virus" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1
370890). RNA. 12 (1): 102–10. doi:10.1261/rna.2129806 (https://doi.org/10.1261%2Frna.21
29806). PMC 1370890 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1370890).
PMID 16301601 (https://pubmed.ncbi.nlm.nih.gov/16301601).
8. Weil JE, Hadjithomas M, Beemon KL (March 2009). "Structural characterization of the Rous
sarcoma virus RNA stability element" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC26437
15). J. Virol. 83 (5): 2119–29. doi:10.1128/JVI.02113-08 (https://doi.org/10.1128%2FJVI.021
13-08). PMC 2643715 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643715).
PMID 19091866 (https://pubmed.ncbi.nlm.nih.gov/19091866).
9. Johnson M, Morris S, Chen A, Stavnezer E, Leis J (2004). "Selection of functional mutations
in the U5-IR stem and loop regions of the Rous sarcoma virus genome" (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC428589). BMC Biol. 2: 8. doi:10.1186/1741-7007-2-8 (https://doi.
org/10.1186%2F1741-7007-2-8). PMC 428589 (https://www.ncbi.nlm.nih.gov/pmc/articles/P
MC428589). PMID 15153244 (https://pubmed.ncbi.nlm.nih.gov/15153244).
10. Wills JW, Cameron CE, Wilson CB, Xiang Y, Bennett RP, Leis J (October 1994). "An
assembly domain of the Rous sarcoma virus Gag protein required late in budding" (https://w
ww.ncbi.nlm.nih.gov/pmc/articles/PMC237081). J. Virol. 68 (10): 6605–18.
doi:10.1128/JVI.68.10.6605-6618.1994 (https://doi.org/10.1128%2FJVI.68.10.6605-6618.19
94). PMC 237081 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC237081). PMID 8083996
(https://pubmed.ncbi.nlm.nih.gov/8083996).
11. Nadaraia-Hoke S, Bann DV, Lochmann TL, Gudleski-O'Regan N, Parent LJ (March 2013).
"Alterations in the MA and NC domains modulate phosphoinositide-dependent plasma
membrane localization of the Rous sarcoma virus Gag protein" (https://www.ncbi.nlm.nih.go
v/pmc/articles/PMC3592118). J. Virol. 87 (6): 3609–15. doi:10.1128/JVI.03059-12 (https://do
i.org/10.1128%2FJVI.03059-12). PMC 3592118 (https://www.ncbi.nlm.nih.gov/pmc/articles/P
MC3592118). PMID 23325682 (https://pubmed.ncbi.nlm.nih.gov/23325682).
12. Einfeld D, Hunter E (November 1988). "Oligomeric structure of a prototype retrovirus
glycoprotein" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC282525). Proc. Natl. Acad. Sci.
U.S.A. 85 (22): 8688–92. Bibcode:1988PNAS...85.8688E (https://ui.adsabs.harvard.edu/abs/
1988PNAS...85.8688E). doi:10.1073/pnas.85.22.8688 (https://doi.org/10.1073%2Fpnas.85.2
2.8688). PMC 282525 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC282525).
PMID 2847170 (https://pubmed.ncbi.nlm.nih.gov/2847170).
13. Gilbert JM, Mason D, White JM (October 1990). "Fusion of Rous sarcoma virus with host
cells does not require exposure to low pH" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2
48002). J. Virol. 64 (10): 5106–13. doi:10.1128/JVI.64.10.5106-5113.1990 (https://doi.org/10.
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14. Dahlberg JE, Sawyer RC, Taylor JM, Faras AJ, Levinson WE, Goodman HM, Bishop JM
(May 1974). "Transcription of DNA from the 70S RNA of Rous sarcoma virus. I. Identification
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C355423). J. Virol. 13 (5): 1126–33. doi:10.1128/JVI.13.5.1126-1133.1974 (https://doi.org/1
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External links
the Rous sarcoma virus (RSV) at rcn.com (http://users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/R/RSV.html) Archived (https://web.archive.org/web/20060429060241/http://users.rcn.c
om/jkimball.ma.ultranet/BiologyPages/R/RSV.html) 2006-04-29 at the Wayback Machine
molecular expressions at magnet.fsu.edu (http://micro.magnet.fsu.edu/primer/techniques/fluo
rescence/gallery/cells/cv1/cv1cells.html) Archived (https://web.archive.org/web/2006021305
5803/http://micro.magnet.fsu.edu/primer/techniques/fluorescence/gallery/cells/cv1/cv1cells.h
tml) 2006-02-13 at the Wayback Machine
Rous+sarcoma+virus (https://meshb.nlm.nih.gov/record/ui?name=Rous+sarcoma+virus) at
the US National Library of Medicine Medical Subject Headings (MeSH)
Rfam entry for retroviral 3'UTR stability element (http://rfam.org/family/RF01417)

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