After being infected with simian
immunodeficiency virus (SIV) in a laboratory study, rhesus macaques that had
more of a certain type of immune cell in their gut than others had much lower
levels of the virus in their blood, and for six months after infection were
better able to control the virus.
SIV is
a retrovirus that
infects primates.
Strains of SIV that
crossed over to humans resulted in the evolution of HIV. In rhesus macaques, SIV
causes simian AIDS (though in many primates it is harmless) and studying the
virus in these animals offers crucial insights into how HIV acts in humans, the
researchers said.
The
discovery by researchers at UCSF may shed light on the mystery of why some
people infected with HIV are better able to control the virus, live longer and
have fewer associated health problems than
others who have been infected as long, they said. It also provides a potential
new target for
developing therapies or vaccines.
The
cells that have the protective effect, called Th17 (T helper 17) cells, are a
subset of the type of disease-fighting immune cell targeted and killed by HIV
and found in the gut of both primates and humans.
A prior
study from the same UCSF team found that SIV infection causes a normally
protective immune response to infection to go awry, leading to reduction in the
protective activity in the gut of these Th17 cells and weakening of mucosal
defenses against bacteria. Interestingly, in that study, Th17 cells were not
affected by SIV in another primate, African green monkeys, in which
SIV infection is harmless and does not cause disease.
"Animals
with more of these Th17 cells were better able to control SIV and this was due
in part to macaques developing a more effective immune response by producing
more SIV-specific CD4-positive T-cells to fight the infection. Our next step is
to see if we can augment the Th17 effect, perhaps by looking at interleukin 17
(IL-17), the cytokine released
by these cells, and testing to see if it has an effect," said the study's
primary investigator, Dennis Hartigan-O'Connor, MD, PhD, assistant professor of
medicine at the UCSF Division of Experimental Medicine.
"Further,
if a treatment can be developed to increase Th17 cells in the gut, it may allow
for a more effective immune response after exposure to an HIV vaccine or the
virus itself," he added.
The
findings are being published in the May 30, 2012 issue of Science
Translational Medicine.
In the
new study, the investigators first determined the levels of Th17 cells in the
gut of sixteen rhesus macaques and then infected them with SIV. They found that
the animals with more Th17 cells to begin with were better able to control the
virus. They then gave animals drugs that deplete Th17 cells and found that
reducing the number of Th17 cells made controlling SIV more difficult for those
animals.
"We
found great variation in the levels of Th17 cells, with as much as a five-fold
difference in numbers between animals. We are not sure why this is the case. It
could be genetically determined or perhaps due to a previous exposure to a type
of bacteria that stimulates production of Th17 cells," said
Hartigan-O'Connor.
This
study is part of a series of investigations undertaken by researchers at the
UCSF Division of Experimental Medicine into how SIV, and by extension HIV,
interacts with the immune system in the gut.
The
previous study was focused on chronic infection and persistent inflammation in
the gut.
"The
earlier study addressed the cause and consequence of inflammation after
infection. We found that inflammation induces an enzyme that knocks out Th17
cells, which normally help to keep the gut intact, and that disease progression
was faster. Reciprocally, we have now found that animals do better if they have
many Th17 cells at the outset of infection. We are gradually increasing our
understanding of this important aspect of the immune system and we are working
to translate this understanding into an approach that benefits patients,"
said study senior author, Joseph M. McCune, MD, PhD, chief of the UCSF Division
of Experimental Medicine.
Study
co-investigators include Bittoo Kanwar from UCSF Division of Experimental
Medicine and Kristina Abel and Koen K. A. Van Rompay from the University of
California, Davis.
Provided
by University
of California, San Francisco
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