Coverage of 2006 International
Conference on AIDS
August 14–18, 2006, Toronto, Canada
Interactions Between HIV and the Immune System
Paul Dalton, Treatment Advocate, Project Inform
August 15, 2006
Today sessions focused on the interactions between the virus and
the immune system.
APOBEC3G
All of us carry with us a powerful anti-HIV enzyme called APOBEC3G.
Over the past few years, scientists have been studying this enzyme,
trying both to understand how it works and, perhaps more importantly,
how HIV overcomes it. Warner Green of the Gladstone Institute for
Virology discussed research on this subject done by his group.
In order to facilitate the development of new drugs to treat HIV,
much of the work he and other scientists are doing is to more completely
understand the activity of APOBEC3G and the HIV gene Vif which overcomes
it. Vif interferes with the activity of APOBEC3G in two ways. First,
it binds to APOBEC3G in such a way that cellular machinery—called
proteasomes—degrades or breaks it down. Second, the HIV gene
Vif signals the cell to produce less of the anti-HIV enzyme APOBEC3G—a
process called down regulation. The combined effect of Vif is the
almost total depletion of APOBEC3G from cells. Finding ways to interfere
with the interaction between Vif and APOBEC3G is an attractive target
for anti-HIV drug development. If you can keep Vif from attaching
to the natural anti-HIV enzyme APOBECG3, it should be able to persist
at high enough levels in the cell to block the virus.
Possibly even more interesting was Green’s groups findings
on the role of APOBEC3G in resting T cells vs. active T cells. It
has long been known that most HIV infection happens in resting T
cells, but that those infections are unproductive—that is,
they do not support further HIV replication. His group discovered
that resting and active T cells have different forms of APOBEC3G
in them. Resting T cells, which are highly resistant to productive
HIV infection, contain high levels of APOBEC3G in its simplest forms—called
monomers or dimers. Active T cells contain little or no APOBEC3G
in this form, but instead contain it in a highly complex form, tied
together with many other proteins and genetic material.
In the simple (or low molecular weight) form, APOBEC3G has potent
anti-HIV effect. In the complex (or high molecular weight) form,
it is basically inactive against HIV. This finding may go a long
way to understanding why resting T cells are resistant to HIV infection.
Further research showed that the highly complex form likely has
important functions, so the ultimate answer won’t be to simply
break the big form into a bunch of little ones, but more likely
find a way to balance the complex and simple forms of the APOBEC3G
protein, so active T cells can successfully resist HIV infection.
GVB-C: a helpful virus?
Once called the Hepatitis G Virus, it was shown awhile back that
people co-infected with HIV and GVB-C seemed to enjoy somewhat better
health compared to people only infected with HIV. This curious observation
has led to a fair amount of research on this seemingly benign virus.
In a poster discussion, Isabella Abbate presented findings showing
that people with GVB-C had more activation of the interferon system
than those without GVB-C. (Interferons are natural antiviral immune
system chemicals.) The research is far from fully explaining the
possible protective role that GVB-C plays in HIV, but it advances
our understanding and serves as the basis for further research that
may lead to ways to help our immune systems better control HIV.
HIV-2
One last interesting presentation was on the differences between
HIV-1 and HIV-2. These two viruses are closely related, but it well
established that HIV-1 is far more aggressive and disease-causing
and is the source of the vast majority of HIV infections worldwide.
David Marchant presented results from an experiment that showed
a distinct difference between the two viruses. In his experiment,
HIV-2 went through a burst of high level replication two days after
it was put into cells and then slowed down to a much lower level
of replication by the third day. In contrast, HIV-1 maintained a
steadier amount of replication throughout the course of the experiment.
Tomorrow
On the schedule for Wednesday are sessions on Hepatitis Co-Infections,
Cytokines, and Structured Treatment Interruptions.
