- NEW YORK (Reuters
Health) - Specialized white blood cells that can crawl around the body
gobbling up invaders--known as macrophages--may play a more important role
in HIV infection than scientists previously thought, researchers said this
week. The findings could have implications for the type of drugs that are
needed to completely eliminate the virus from an infected person.
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- The combinations of drugs currently used to fight HIV
can reduce levels of virus in the body, but the virus usually rebounds
after the drugs are stopped. Because HIV attacks one type of white blood
cell--CD4 T-cells--early in the infection, researchers have thought that
these cells were likely to be the source of the rebounding virus. But the
new results suggest that macrophages, not CD4 T cells, may be where the
virus springs from later in the disease.
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- Macrophages are on the frontlines of the immune system,
gobbling up invaders and displaying the interloper's proteins on their
surface--a step that normally triggers the immune system to attack the
invader.
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- Dr. Malcolm A. Martin, from the National Institute of
Allergy and Infectious Diseases in Bethesda, Maryland and colleagues infected
monkeys with a hybrid HIV-like virus called SHIV and used a range of techniques
to identify which cells and tissues the virus infected.
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- The deadly hybrid killed CD4 T cells in the blood within
3 weeks of infection. But the animals survived 3 to 6 additional months,
producing extremely high levels of virus--suggesting that viruses were
``hiding'' in some other cells.
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- Measurements of viral genetic material showed evidence
of the virus in macrophages scattered throughout the lymph nodes, gastrointestinal
tract, spleen, liver and kidney, the researchers note in an online report
in the January 2nd Early Edition of the Proceedings of the National Academy
of Sciences.
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- As in humans, anti-HIV drug therapy early in infection
reduced the viral levels in the monkeys. In contrast, reverse transcriptase
inhibitor treatment during the macrophage stage of the infection did not
reduce virus levels, the authors write.
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- ``Our research suggests that macrophages are an underappreciated
reservoir of virus in HIV infection,'' Martin said in a statement.
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- ``These cells become infected immediately after exposure
to HIV, are relatively resistant to virus killing, and are able to produce
lots of new virus. Most currently available treatments target HIV during
its infection of T cells, but if the virus also infects and accumulates
in large amounts in macrophages, additional drugs may be required,'' he
added.
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- ``Our studies suggest that we need new classes of antiretroviral
agents that can target HIV during infections of tissue macrophages,'' the
researcher noted. ``They potentially could eliminate this reservoir of
virus and obviously complement currently available drugs.''
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- SOURCE: Proceedings of the National Academy of Sciences,
USA (online) January 2, 2001;doc 5517.
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