METH PROMOTES SPREAD OF VIRUS IN HIV-INFECTED USERS

BUFFALO, N.Y. -- Researchers at the University at Buffalo have
presented the first evidence that the addictive drug methamphetamine,
or meth, also commonly known as "speed" or "crystal," increases
production of a docking protein that promotes the spread of the HIV-1
virus in infected users.

The investigators found that meth increases expression of a receptor
called DC-SIGN, a "virus-attachment factor," allowing more of the
virus to invade the immune system.

"This finding shows that using meth is doubly dangerous," said
Madhavan P.N. Nair, Ph.D., first author on the study, published in
the online version of the Journal of Neuroimmune Pharmacology. The
study will appear in print in the September issue of the journal.

"Meth reduces inhibitions, thus increasing the likelihood of risky
sexual behavior and the potential to introduce the virus into the
body, and at the same time allows more virus to get into the cell,"
said Nair, professor of medicine and a specialist in immunology in
the UB School of Medicine and Biomedical Sciences.

His research centers on dendritic cells, which serve as the first
line of defense again pathogens, and two receptors on these cells --
HIV binding/attachment receptors (DC-SIGN) and the meth-specific
dopamine receptor. Dendritic cells overloaded with virus due to the
action of methamphetamine can overwhelm the T cells, the major target
of HIV, and disrupt the immune response, promoting HIV infection.

"Now that we have identified the target receptor, we can develop ways
to block that receptor and decrease the viral spread," said Nair. "We
have to approach this disease from as many different perspectives as possible.

"If we could prevent the upregulation of the meth-specific dopamine
receptor by blocking it, we may be able to prevent the interaction of
meth with its specific receptors, thereby inhibiting the virus
attachment receptor," said Nair.

"Right now, we don't know how the virus-attachment receptor and
meth-specific receptors interact with each other, leading to the
progression of HIV disease in meth-using HIV-infected subjects. That
is the next question we want to answer.

"Since meth mediates its effects through interacting with dopamine
receptors present on the cells, and meth increases DC-SIGN, which are
the HIV attachment receptors, use of dopamine receptor blockers
during HIV infection in meth users could be beneficial
therapeutically to reduce HIV infection in these high-risk
populations," Nair said.

Additional researchers on the publication, all from the UB Department
of Medicine, are Supriya Mahajan, Ph.D., research assistant
professor; Donald Sykes, Ph.D., research associate professor; Meghana
V. Bapardekar, Ph.D., postdoctoral associate, and Jessica L.
Reynolds, Ph.D., research assistant professor.

The University at Buffalo is a premier research-intensive public
university, the largest and most comprehensive campus in the State
University of New York. The School of Medicine and Biomedical
Sciences is one of five schools that constitute UB's Academic Health Center.