Tuesday, November 22, 2016

Reverse Engineering the Weaponry of Retroviruses

      With all the observed diversity of life on our planet, it should come as no surprise that algae are not the only things to be subsumed into the processes of complex organisms. One such 'thing', retrovirses, invaded the cells of our ancestors about 50 million years ago, and are estimated to make up between 6 and 8 percent of the human genome. Endogenous retroviruses are fragmentary remnants of a retrovirus' genome that have been conserved and re-purposed, to the benefit of the host. Millennia of having alien DNA interted into our genomes has resulted not in the acquisition of new organelles, but the co-opting of the virus's mode of reproduction: its DNA.

Early phases of retrovirus life cycle with stages of inhibition labeled.

      In the distant 90's, British researchers discovered a protein called Fv1 in mice. This protein protected the mouse from Murine Leukemia Virus (MLV) by post-entry amino acid substitution of the capsid protein known as Ca. Alteration of the capsid prevents the newly transcribed viral DNA from entering and being integrated into the host nucleus (1.) Analysis of the protein revealed that it was controlled by an endogenous retrovirus.
     This led researchers Cedric Feschotte, Edward Chuong, Nels Elde to wonder if human beings used ERs in a similar fashion. To answer this question, they looked instead at retroviruses located very close to genes that are activated by the protein interferon, which regulates immune response.  After the retroviruses were edited out, the human cells were exposed interferon. The genes were found to be nearly inactive. This suggested a different role for retroviruses: they acted as on/off switches for other genes in the interferon pathway.
     There seems to be a great deal of work ahead in this area of study. What is the mechanism of retention for these retroviruses? How does a cell weed out the useless genes?
If anyone is interested in reading the original paper 'Fv1, the Mouse Retrovirus Resistance Gene' by J.P Soye- it is available by request through iLLiad by that title.

Study Finds Surprising Benefit of Viral DNA: Fighting Other Viruses

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