IMMUNE CELLS PROPOSED AS HIV HIDE OUT DON'T LAST IN PRIMATE MODEL
Where does HIV hide?
Antiretroviral drugs can usually control the virus, but can't completely
eliminate it. So any strategy to eradicate HIV from the body has to take into
account not only the main group of immune cells the virus targets, called CD4
or helper T cells, but other infected cells as well.
New
research from Yerkes National Primate Research Center, Emory University, sheds
light on the question of which cells support viral replication and persistence,
and the answers have implications for future efforts to eliminate HIV from the
body in human patients.
The results were published Oct. 30 in the journal PLOS
Pathogens.
"Our results have implications for efforts to cure
HIV," says lead author Mirko Paiardini, PhD, assistant professor of
pathology and laboratory medicine at Emory University School of Medicine and
Yerkes National Primate Research Center. "Our findings suggest that
therapeutic strategies aimed at stimulating infected macrophages may facilitate
viral elimination."
Researchers at Yerkes looked at what happens when rhesus
macaques have CD4 T cells removed from their immune systems before infection by
HIV's cousin SIV. They found that another type of immune cell, called
macrophages, then becomes heavily infected by SIV. Infected cells are present
in lymph nodes, intestine and brain as well as in the blood.
However, the macrophages live shorter than expected based on
previous research studies, which calls into question the idea that the
macrophages could serve as a long-term hideout when someone is infected by HIV
but receiving antiretroviral drugs.
"Among HIV researchers, there has been a lot of debate about
the contribution of macrophages to the HIV reservoir," Paiardini says.
"We show that in the absence of CD4 T cells, macrophages can be heavily
infected by SIV, which supports a role for macrophages in viral infection.
However, when infected at high levels, macrophages become short-lived cells in
vivo, with an average lifespan of 1.3 days. Thus, if validated in the setting
of HIV infection in humans, our data support a model in which macrophages do
not constitute the long-lived reservoir (in order of weeks) that has been
proposed."
The researchers also found evidence that in macaques with
depleted CD4 T cells, SIV is infecting microglial cells in the brain, otherwise
rarely seen.
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