Scientists from Yerkes National Primate Research Center and the Emory Vaccine Center have all but determined why SIV and HIV infection leads to AIDS in some primate species but not in others.
Studying the mangabeys, the natural hosts for the AIDS viruses that remain healthy despite SIV infection, the researchers have found that heir immune systems are activated to a significantly lower extent during the infection than are the immune systems of rhesus macaques.
The researchers say that this difference may explain why SIV and HIV infection leads to AIDS in some primate species but not others.
"During both HIV infection in humans and SIV infection in macaques, the host immune system becomes highly activated, experiences increased destruction and decreased production of key immune effector cells and progressively fails as a result. In contrast, natural hosts for SIV infection, like sooty mangabeys, do not exhibit aberrant immune activation and do not develop AIDS despite high levels of ongoing SIV replication," said Mark Feinberg, MD, PhD, the paper's senior author.
"Our studies sought to understand the basis for the very different responses to AIDS virus infections in different species," he added.
The reasons are found in significant differences in immune signaling in a specific type of dendritic cells in AIDS-susceptible or resistant host species.
Dendritic cells are part of the immune system that play a key role in alerting the body to the presence of invading viruses or bacteria, and in initiating immune responses that enable clearance of these infections. They detect the invaders using molecules called Toll-like receptors.
The researchers found that in sooty mangabeys, dendritic cells produce much less interferon alpha--an alarm signal to the rest of the immune system--in response to SIV.
As a result, the dendritic cells are not activated during the initial or chronic stages of SIV infection, and mangabeys fail to mount a significant immune response to the virus.
In contrast to mangabeys, dendritic cells from humans and macaques that are susceptible to developing AIDS are readily activated by HIV and SIV.
The difference in whether or not dendritic cells become activated upon AIDS virus exposure in specific primate hosts appears to result from species-specific differences in patterns of Toll-like-receptor signaling.
Because host immune responses are unable to clear AIDS virus infections, ongoing virus replication leads to unrelenting activation of the immune system in humans and macaques.
Unfortunately, rather than promoting clearance of the infection, chronic dendritic cell stimulation may result in chronic immune activation and significant unintended damage to the immune system in AIDS-susceptible species. Such chronic immune activation is now recognized to be a major driving force for the development of AIDS.
The observation that mangabey dendritic cells are less susceptible to activation by SIV may explain why mangabeys do not exhibit abnormal immune activation and do not develop AIDS.