15 July 2010 HIV/AIDS OUTLOOK

The primate and macaques could be the loss of T-helper 17

(TH17) cells — a subset of CD4 cells that is key
for antibacterial defence. Douek and others

connection
have shown that SIV-infected sooty mangabeys
and African green monkeys have healthy levels
of TH17 cells in the mucus lining of the gastroin-
testinal tract. Loss of these cells is a hallmark of
progressing infection in humans and macaques
Studies comparing HIV infection and its simian (see page S2).
counterpart in different monkey species are filling
Model monkeys
gaps in knowledge, explains Bijal Trivedi. In their search for a surrogate for HIV in

M
humans, researchers use about 20 differ-
ale African green monkeys are CD4 cells in sooty mangabeys have lower lev- ent SIV strains and modified SIVs, dubbed
notorious for their striking red els of the receptor CCR5, which HIV needs SHIVs, to infect different species of macaques.
penis, bright-blue scrotal area to enter the cell. African green monkeys Each virus–host combination has strengths
and white abdomen. To AIDS have fewer surface CD4 receptors, which are and limitations.
researchers, however, these monkeys and required for HIV infection. The main problem with the SIV–macaque
another African species, the sooty mangabey, “They’ve chosen two different ways of model, says Paul Bieniasz, a virologist at the
are known for a less visible trait. removing target cells of the virus,” notes Daniel
Aaron Diamond AIDS Research Center, New
Both are natural hosts of the simian immu- Douek, who leads the Human Immunology York, is that the SIV genome differs by about
nodeficiency virus (SIV), which is the primate Section of the US National Institute of Allergy 50% from HIV-1, which is the most prevalent
counterpart and ancestor of HIV. Although and Infectious Diseases’ Vaccine Research strain worldwide.
infected monkeys have more than 100,000 cop- Center. “I really think that is the root of why To create a better model for vaccine tests,
ies of SIV per millilitre of blood, they do not they don’t progress [to AIDS].” Bieniasz and colleagues are modifying HIV-1
get sick or develop anything resembling AIDS. Viral load is not the only factor influenc-
to grow in monkeys. So far, they have created
By contrast, Asian macaques infected with SIV ing progression. People with low levels of a version that will infect pigtail macaques,
mimic the trajectory of human HIV infection. HIV sometimes show serious inflammation initially causing virus levels to reach up to
Understanding what allows and a slow decline in CD4 one million copies per millilitre of blood — just
the African monkeys to coex- “It is amazing that cells. Some such cases slowly
like in the initial stages of human infection.
ist with SIV could help develop [the monkeys] are progress to AIDS, says Steven These monkeys do not become sick and,
drugs or vaccines against HIV able to switch off Deeks, professor of medicine at
after six months, their infection mimics that
that ape their response. these pathways.” the University of California, San
seen in long-term non-progressors, who

Rod Williams/Naturepl.com
“Comparative AIDS research Francisco. naturally control HIV levels and slow their
is essential to figure out what protects us from “There are people who think it is only theprogression to AIDS (see page S4).
transmission, and what protects us from virus, others think it is only inflammation, and “We basically have to find a way to make the
pathogenesis,” says Guido Silvestri, professor we think it is a little of both,” adds Deeks. virus more robust in pig-tail macaques,” says
of pathology at Emory University. When the virus first infects the body, humans,
Bieniasz. “We need it to trigger AIDS.”  n
SIV infections in the natural host monkeys macaques and natural hosts mount a dramatic Bijal Trivedi is a freelance writer in Washington
share similarities with human HIV and macaque immune response. In sooty mangabeys and DC.
SIV infections; however, it is the differences African green monkeys,
Biosphoto/Cordier Sylvain/BIOSphoto/Still Pictures

that intrigue researchers. For example, unlike this reverts to base-

humans and macaques, female natural hosts line levels after about
rarely pass the virus on to their offspring. three months, whereas
In people, there is a general trend: the more it remains high in
virus in the body, the faster the progression humans and macaques
to AIDS. This is probably why elite control- throughout the chronic
lers, whose immune systems can whittle down infection.
viral loads to barely detectable levels, rarely get “It is amazing that
AIDS (see page S4). By contrast, sooty mang- [the natural hosts] are
abeys and African green monkeys with high able to switch off these
viral loads remain healthy. pathways of immune
What is more, the natural hosts maintain response even when
relatively healthy numbers of CD4 cells — virus replication remains
white blood cells that orchestrate the immune consistently high. And it
response and are targets of HIV — in both blood seems that they benefit
and the mucus lining of the genital tract. from doing this switch
off,” says Silvestri.
Evasive targets One potential trig- African green monkeys (left) and sooty mangabeys (right) are natural
One key to the monkeys’ resilience might be ger for chronic immune hosts of the HIV-like simian immunodeficiency virus, meaning that they
that they have fewer cells that HIV can infect. activation in humans never develop anything resembling AIDS.
www.nature.com/outlooks S5