Study identifies characteristics of HIV-1 strains that mediate sexual transmission.
Upon sexual exposure, the AIDS virus must overcome some mighty barriers to find the right target cell and establish a new infection. It must traverse the genital mucosa and squeeze through tightly packed epithelial cells meant to keep invaders out. And then it must thwart the initial immune-system alarm bell in the form of type 1 interferons. In fact, according to some studies, only about 1 in 1,000 unprotected sexual exposures lead to a successful HIV-1 infection.
“What is unique about these transmitted viruses that make it this far?” asked Beatrice Hahn, MD, a professor of Medicine and Microbiology in the Perelman School of Medicine at the University of Pennsylvania. “The human body has considerable innate barriers that effectively combat virus infections.”
Hahn and colleagues examined the characteristics of HIV-1 strains that were successful in traversing the genital mucosa that forms a boundary to entry by viruses and bacteria. Studying viral isolates from the blood and genital secretions of eight chronically HIV-1 infected donors and their matched recipients, the researchers identified a sub-population of HIV-1 strains with biological properties that predispose them to establish new infections more efficiently.
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The team generated 300 virus isolates from individual HIV-1 particles infecting both the donors and their matched recipients. Compared to viruses isolated from the donors, they found that recipient viruses were three times more infectious, had a 1.4 higher ability to replicate, and were significantly more resistant to the antiviral effects of two type 1 interferons, IFN-alpha2 and IFN-beta.
“This means that rapidly multiplying strains of HIV-1 that are interferon resistant have an increased transmission fitness,” said Shilpa Iyer, a doctoral student in the Hahn lab and a co-first author of the study. “We confirmed this by pretreating CD4 immune cells with interferon prior to virus isolation. In doing this, we were able to select donor isolates that had a transmitted virus-like phenotype.”