New research in monkeys exposed to SIV, the animal equivalent of HIV, reveals what happens in the very earliest stages of infection, before virus is even detectable in the blood, which is a critical but difficult period to study in humans. The findings, published in the journal Cell, have important implications for vaccine development and other strategies to prevent infection.
Researchers exposed 44 rhesus monkeys to SIV and conducted analyses of the animals on days 0, 1, 3, 7 and 10 following exposure, they found that SIV could disseminate rapidly through the body, with viral RNA (SIV's genetic material) present in at least one tissue outside the reproductive tract in most monkeys analyzed 24 hours after exposure.
The inflammatory response occurred in virus-infected tissues soon after exposure to SIV, and increasing amounts of viral RNA correlated with rising amounts of a host protein called NLRX1, which inhibits antiviral immune responses. In addition, the TGF-beta cell-signaling pathway, which suppresses adaptive immune responses, was triggered and correlated with lower levels of antiviral T immune cell responses, as well as higher levels of SIV replication. The researchers observed elevated expression of genes in the TGF-beta pathway in tissues that contained viral RNA as early as day 1 after exposure to the virus.
The findings suggest that there may be a very narrow window of opportunity to contain or eliminate the virus. HIV prevention strategies should take these factors into account. "We believe that these insights into early HIV/SIV infection will be critical for the development of interventions to block infection, such as vaccines, antibodies, microbicides and drugs," author said. "The next step in this line of research is to evaluate how various interventions may impact these early events."