Acutely Transforming Tumor Viruses

Acutely Transforming Retroviruses: These little buggers are awful. “Why?” you may ask. Well acutely transforming retroviruses produce tumors within weeks of infection. When acutely transforming retroviruses infect a cell, they are able to incorporate some of the host cell’s genetic material into their own genome. Then, when the retrovirus infects another cell, it carries this new genetic material with it and integrates this tag-along material along with its own genome into the genome of the next cell.  It will continually repeat this process. This is how the discovery of oncogenes came to light.

Acutely transforming retroviruses account for only a small portion of naturally occurring tumors caused by retroviruses and they have never been isolated from humans. Several properties make them rare in nature, such as the requirement for a helper virus and the acute nature of the malignancies that they cause, which reduces the probability of parallel transmission. How ever, the study of these viruses has played a very important role in the explanation of viral oncogenesis.

The RNA genome has terminal repeats (R), subterminal unique sequences (U5, U3) and three genes, gag, pol and env. A complicated scheme of splicing and post-translational processing results in a variety of protein products. In an acute transforming retrovirus (bottom), one or more of the viral genes is replaced by a transduced cellular sequence, the oncogene. Initially it is translated into a fusion protein.

Rous sarcoma virus (RSV) is the most widely known acutely transforming retrovirus, largely because it was the first one discovered. It was found that RSV from one bird, at the time only known as an element in a filtrate, could transform normal cells into abnormally proliferating cells in a different bird. Researchers found this in the early years of the 20th century but they did not know how the virus could actually do this until 1970. They later found that the gene src was active in transforming viruses. The researchers used a mutant form of Rous sarcoma that was a nontransforming form of the virus that wouldn’t cause tumors. In this way the researchers first determined that src was the first proto-oncogene. But, then the researchers actually found that src was not, in fact, originally a viral gene, but that an ancestor of RSV had “accidentally” picked it up from a host cell during a previous infection. In such a way the researchers discovered that the src gene was really a proto-oncogen and not an oncogene.

http://www.dnatube.com/video/286/The-Rous-Sarcoma-Virus-RSV   ….Sadly It won’t let me embed this video…

Below is the proviral DNA structure of RSV. The line at the top indicates the chromosomal DNA containing proviral DNA. SD indicates the splicing donor site and SA indicates the splicing acceptor site. Three transcripts are produced from the LTR promoter, as shown below.