Rous Sarcoma VirusBY MICKINZIE METZ

Case Study

Bob Rooster is the owner of a chicken farm, one day he noticed some of his chickens were moving stiff, look distressed and were failing to thrive. On one of the first chickens that died the farmer observed masses on its body and sent the chicken away for testing.

In the lab they ground up the tumors and passed then through a filter that not even bacteria can fit through to identify this infection as a virus.

Rous Sarcoma Virus

Class VI enveloped virus Discovered by Peyton Rous in 1911. Awarded Noble Prize for Physiology

or Medicine in 1966. First oncovirus to be described oncoRNA viruses are called simple viruses whereas a virus like HIV is a

complex retrovirus Simple retroviruses only contain the gag, pol and env genes Simple viruses encode only singly spliced or unspliced RNA

Entry

Need one or more receptors Env proteins have a N term SU unit involved in receptor binding and a C

term TM unit which is a trans-membrane anchor. They are metastable structures.

When Env binds to its receptor, the SU dissociates from the TM, exposing the fusion peptide. The fusion peptide inserts into the target cell membrane

Hemifusion intermediate: In the endosome the heptad repeats “zipper back” folding into six helical bundles, pulling the cell and viral membranes closer.

Entry

Replication

Fusion releases the retroviral core into the cytoplasm Reverse transcription takes place within the viral cores Result is double stranded DNA copy transported to the nucleus and

integrated into the host chromosome. Host RNA pol II transcribes cDNA into mRNA as well as progeny viral

genomes

Replication

Has only 4 genes gag, which encodes the capsid protein pol, which encodes the reverse transcriptase env, which encodes the envelope protein src, which encodes a tyrosine kinase, an enzyme that

attaches phosphate groups to Tyr residues on a variety of host cell proteins. This is what causes the virus to be oncogenic.

Integration

Full picture

Treatment

Since the oncogenic activation of the virus is still being studied there is no effective treatment at the time.

Research is being conducted to study the influence of 2',5' adenosine nucleotides on the replication and transformation of cells by Rous sarcoma virus (RSV). Treatment with certain nucleotides, ppp2',5'A4 and 2',5'A4, causes a striking reduction (50-fold) in the yield of infectious progeny virus. With this reduction it could possibly knock out the oncogenic gene.

References

Kimboll’s Biology Pages (2015). http://www.biology-pages.info/R/RSV.html

The Journal of Experimental Medicine (2011). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256973/

PubMed (2012). https://www.ncbi.nlm.nih.gov/pubmed/6191438