Why not all HIV progresses to AIDS in non-human primates
Washington, Sept 17 : A team of scientists from Yerkes National Primate Research Center
and the Emory Vaccine Center has reached a step closer to determining why SIV and HIV
infection leads to AIDS in some primate species but not others.
Studying the mangabeys, the natural hosts for the AIDS viruses that remain healthy
despite SIV infection, the researchers have found that
their 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.
--ANI
