Seeking to shed new light on HIV's ability to survive in the body and cause disease, the National Institute of Allergy and Infectious Diseases at the NIH has awarded a five-year, $1.9 million grant to an AIDS research team at the College of Dentistry to continue its study of a new mode of HIV replication that involves cooperation between viruses.
The team leader, Dr. David N. Levy, an Assistant Professor of Basic Science and Craniofacial Biology, discovered the mechanism in an earlier study he conducted with the assistance of a one-year pilot grant from CFAR, The Center for AIDS Research at the NYU School of Medicine.
HIV normally inserts its DNA into the DNA of the cells it infects in a process called integration that is inefficient and prone to failure, and can result in an aborted virus replication cycle. As a result, up to 99 percent of HIV DNA is found in an unintegrated form. Although the abundance of unintegrated DNA has long been known, its biological significance has not been clear.
In a paper published in the July 2008 issue of the journal Retrovirology, Dr. Levy and his team demonstrated that the unintegrated viruses can, in fact, replicate when they are assisted or "complemented" by viruses that successfully integrate with the DNA of infected cells. Dr. Levy believes that this newfound cooperation among HIV viruses helps HIV persist in the body and evade immune responses.
"HIV rapidly mutates and evolves during infection, which prevents the immune system from successfully stopping virus replication" explains Dr. Levy, "and we have shown that these cooperative interactions speed up the evolution of the virus by increasing the amount of genetic exchange between viruses through a process called recombination."
"Previous work from my laboratory demonstrated that recombination between viruses occurs frequently, and our most recent study reveals that recombination is likely to be even more frequent than was previously thought."
"This new mode of virus replication has implications for many aspects of HIV biology and disease. Our expectation is that by better understanding this previously unknown mode of HIV replication, we can find new ways of slowing or stopping HIV replication and the disease it causes."
Dr. Dominik Wodarz, a Professor of Ecology and Evolutionary Biology at the University of California at Irvine, is a coinvestigator on the grant.