2005 - Jefferson virologists coax HIV out of hiding
EurekAlert!
When researchers came up with the powerful cocktail of anti-HIV drugs known as highly active antiretroviral therapy (HAART), they hoped they had found a way to finally rid the body of the virus. But they were wrong. The virus instead goes into hiding, dormant and practically undetectable in the body ? and impervious to attack. While HAART manages to keep the virus at bay, it's still quite capable ? given the right opportunity ? of replicating and wreaking havoc on the body's immune system.
Now, virologists at Jefferson Medical College, led by Roger J. Pomerantz, M.D., professor of medicine, biochemistry and molecular pharmacology and director of the Division of Infectious Diseases and Environmental Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, may have found a way to bring HIV out of hiding. They have shown that an immune cell protein called interleukin-7 (IL-7) can rouse the virus better than previously tried agents, making it vulnerable to drugs and the body's immune system. If the new technique proves its mettle, the work could lead to improved treatments for HIV infection, and might be a step toward complete viral eradication.
The Jefferson team reports its findings January 4, 2005 in the Journal of Clinical Investigation.
Dr. Pomerantz, who is director of Jefferson's Center for Human Virology and Biodefense, and his co-workers took blood cells from HIV-infected patients who had been taking HAART and who had undetectable levels of virus. Using a special technique, they screened the cells with several different drugs to determine what stimulated the latent virus the best.
"To our surprise, it was IL-7," he says. "We don't know why, but it is the best agent in terms of its ability to stimulate HIV out of latency that we've seen in the last 15 years." They found that the virus was stimulated to higher levels and was activated in more patients than with other compounds.
Dr. Pomerantz's group also discovered that IL-7 appears to stimulate a group of sub-strains of HIV that are different than those brought out of latency by other agents, such as IL-2, another immune cytokine, or OKT3, a monoclonal antibody. He suspects such strains may be from an unknown viral reservoir in the blood.
"IL-7 may teach us something," he says. "We're not sure why only these certain strains are affected. We think we've found a new population, a new reservoir of HIV that has not been seen before. It's probably a sub-population of blood cells, lymphocytes not stimulated by IL-2 or OKT3. There could be other reservoirs as well."
Ultimately, he says, the answer to the latency problem may entail using a combination of drugs. "We may need more than one drug to stimulate virus from latency, similar to using HAART to stop replication," he says, referring to this approach . "We may have to combine IL-2 with IL-7 and other agents to get to the reservoirs of virus."
omniomix.com
Second article
IL-7 wipes out HIV-1 hideouts
In the January 3 issue of the Journal of Clinical Investigation, Roger Pomerantz, Giuseppe Nunnari, and colleagues from Thomas Jefferson University demonstrate that the growth factor IL-7 is a unique, potent, and strain-specific inducer of latent HIV-1 activation in infected individuals on virally suppressive HAART. IL-7, a molecule that promotes the growth and activation of B and T cells, was shown to also stimulate HIV-1 activation from resting T cells in order to deplete pools of HIV-1?infected cells. The authors show that a distinct viral species is activated by IL-7, and suggest that different molecules may deplete only a specific proportion of the latent HIV-1 population in individuals on HAART. IL-7 could potentially be combined with other molecules to potentially delete reservoirs of HIV-1 in new antiretroviral approaches.
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TITLE: IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART
AUTHOR CONTACT: Roger Pomerantz
Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Phone: 215-503-8575; Fax: 215-503-2624; E-mail: Roger.J.Pomerantz@jefferson.edu.
A PDF of this article this article is available at: jci.org.
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