Thursday, February 21, 2008

A Human Endogenous Retrovirus Reconstituted

Remember those HERVs we talked about in the previous post? A group from the Aaron Diamond AIDS Research Center at The Rockefeller University has reconstituted one of them using molecular techniques. The entire article is published in PLOS Pathogens, a free, full text, on-line journal.

These investigators have reconstitute a Class II HERV, HERV-K.
A pseudo-ancestral HERV-K DNA sequence was synthesized and used to produce viral proteins and RNA that could reconstitute the HERV-K replication cycle. Thus, the replication and biology of a once-extinct retrovirus can now be studied in the laboratory. Interestingly, reconstituted HERV-K replication experiments, and comparison of the reconstituted HERV-K DNA sequence with the dead HERV-Ks in modern human DNA, suggests that HERV-K may have been extinguished in humans in part by host defenses that induce mutation of retroviral DNA and that the reconstitution of the pseudo-ancestral HERV-K reversed these changes.
This further suggests that infection with ancient retroviruses induced selective pressure on the human immune system allowing us to resist infection with certain retroviruses.
Two major components of intrinsic defense against retrovirus and retroelement replication in primate cells are the TRIM5 and APOBEC3 gene products [40–42]. Analysis of these genes in modern primates indicates that these genes have likely been under positive selection pressure for significant portions of primate evolution [12–16]. As an endogenous retrovirus that has also apparently replicated exogenously and has been active for much of Old World primate evolutionary history, HERV-K is an excellent candidate for an agent that has imposed sustained evolutionary pressure on antiretroviral defenses present in modern primates.
The Introduction and Discussion in this article is very readable. Give it a try.

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