Window of Opportunity Against HIV Comes from 'fitness bottleneck'
Jul 11, 2014 - 11:01:18 AM
HIV represents evolution on overdrive. Every infected individual contains a swarm of viruses that exhibit variability in their RNA sequence, and new mutations are constantly appearing. Yet nearly every time someone new is infected, this diverse population of viruses gets squeezed down to just one individual.
The genetic bottleneck effect was known, but now the selection for viral fitness driving it is becoming clear. Researchers have found that viral protein sequences matching a consensus sequence, which is hypothesized to be most fit, are more likely to be transmitted than those that deviate from the consensus.
The results were published Thursday in Science.
"The best explanation for what we are seeing is that frequently, after exposure to HIV, a few cells in the genital tract are infected, without establishment of a systemic infection," says senior investigator Eric Hunter, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine, Emory Vaccine Center, and Yerkes National Primate Research Center. Hunter is a Georgia Research Alliance Eminent Scholar and co-director of the Emory Center for AIDS Research.
"We now have evidence that the game isn't lost as soon as the first target cell is infected. It suggests that any approach that makes it more difficult for the virus to replicate in a cell, or that targets infected cells for killing before they can release new viruses, will reduce the probability of systemic infection."
Scientists led by Hunter at Emory Vaccine Center/Center for AIDS Research teamed up with lead author Jonathan Carlson, PhD, and colleagues at Microsoft Research. The team collaborated with Susan Allen, MD, MPH, director of the Zambia-Emory HIV Research Project, and HIV prevention programs in Zambia that enroll heterosexual couples with one HIV-positive partner. These programs provide counseling and condoms, but HIV transmission still occurs despite a two-thirds reduction in the infection rate.
Regular blood tests and close monitoring allowed the researchers to compare the virus that gets transmitted to the viruses in the chronically infected partner, for 137 transmission events over 10 years. Further monitoring in the first two years of infection permitted the team to track the effects of viral mutations.
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