Rous sarcoma virus
Encyclopedia
Rous sarcoma virus 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 cDNA before integration into the host DNA.
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).
Rous was awarded the Nobel Prize
for the significance of his discovery in 1966.
RSV has three genes:
(It lost the env gene normally seen in avian retroviruses during the recombination events that allowed it to acquire src)
The RSV genome has terminal repeats enabling its integration into the host genome and also overexpression of RSV genes.
is oncogenic
as it triggers uncontrolled growth in abnormal host cells. It is an acquired gene, found to be present throughout the animal kingdom
with high levels of conservation between species.
The src gene was taken up by RSV and incorporated into its genome
conferring it with the advantage of being able to stimulate uncontrolled mitosis
of host cells, providing abundant cells for fresh infection
.
The src gene is not essential for RSV proliferation
but it greatly increases virulence
when present.
that ranges between 5–7 kb in length which would usually direct it toward nonsense mediated decay
(NMD) within the eukaryotic host cell. A conserved secondary structure
element has been identified within the 3'UTR and is known as the Rous Sarcoma Virus Stability Element (RSE). This element has been shown to prevent the degradation of the unspliced
viral RNA
The RSE element was first identified in the genome of the Rous Sarcoma Virus but appears to be widely conserved across the avian retrovirus family. The RSE element is ~300 bp in length and located downstream of the gag natural translational termination codon. The secondary structure of the RSE element has been determined by RNAse digestion and SHAPE chemistry analysis.
Other elements that have been identified in RSV include a primer binding site
.
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
and is the first oncovirus
Oncovirus
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely-transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor...
to have been described: it causes sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...
in chickens.
As with all retroviruses, it reverse transcribes its RNA genome into cDNA before integration into the host DNA.
History
RSVRSV
RSV may refer to:* Respiratory syncytial virus, a virus causing respiratory disease* Revised Standard Version, an English Bible translation* Right subclavian vein* Rous sarcoma virus, a retrovirus causing cancer in chickens* Royal Society of Victoria...
was discovered in 1911 by Peyton Rous, working at Rockefeller University
Rockefeller University
The Rockefeller University is a private university offering postgraduate and postdoctoral education. It has a strong concentration in the biological sciences. It is also known for producing numerous Nobel laureates...
in New York City, by injecting cell free extract of chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
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).
Rous was awarded the Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
for the significance of his discovery in 1966.
Structure and genome
RSV is a class VI enveloped virus with a positive sense RNA genome having a DNA intermediate.RSV has three genes:
- gag - encodes capsid proteins
- pol - encodes reverse transcriptase
(It lost the env gene normally seen in avian retroviruses during the recombination events that allowed it to acquire src)
- srcSrc (gene)Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...
- encodes a tyrosine kinaseTyrosine kinaseA tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
that attaches phosphate groups to the amino acid tyrosineTyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
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
The src geneSrc (gene)
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...
is oncogenic
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
as it triggers uncontrolled growth in abnormal host cells. It is an acquired gene, found to be present throughout the animal kingdom
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
with high levels of conservation between species.
The src gene was taken up by RSV and incorporated into its genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
conferring it with the advantage of being able to stimulate uncontrolled mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
of host cells, providing abundant cells for fresh infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
.
The src gene is not essential for RSV proliferation
Proliferation
Proliferation may refer to:*Nuclear proliferation*Chemical weapon proliferation*Cell proliferation* The proliferative phase of wound healing...
but it greatly increases virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
when present.
RNA secondary structure
The RNA genome of RSV contains an extremely long 3' UTRThree prime untranslated region
In molecular genetics, the three prime untranslated region is a particular section of messenger RNA . It is preceeded by the coding region....
that ranges between 5–7 kb in length which would usually direct it toward nonsense mediated decay
Nonsense mediated decay
Nonsense-mediated decay is a cellular mechanism of mRNA surveillance that functions to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. Following transcription, precursor mRNA undergoes an assemblage of ribonucleoprotein components followed by regulatory...
(NMD) within the eukaryotic host cell. A conserved secondary structure
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
element has been identified within the 3'UTR and is known as the Rous Sarcoma Virus Stability Element (RSE). This element has been shown to prevent the degradation of the unspliced
RNA splicing
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...
viral RNA
The RSE element was first identified in the genome of the Rous Sarcoma Virus but appears to be widely conserved across the avian retrovirus family. The RSE element is ~300 bp in length and located downstream of the gag natural translational termination codon. The secondary structure of the RSE element has been determined by RNAse digestion and SHAPE chemistry analysis.
Other elements that have been identified in RSV include a primer binding site
Rous sarcoma virus (RSV) primer binding site (PBS)
This family represents a structured region around the Rous sarcoma virus primer binding site . This region is known to be required for the efficient initiation of reverse transcription....
.