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Scientists find HIV-blocking protein in monkeys

Scientists at the Dana-Farber Cancer Institute have identified a protein that blocks HIV replication in monkey cells. Humans have a similar protein, although it is not as effective at stopping HIV, say the researchers whose work is published in this week's issue of Nature. The team, headed by Joseph Sodroski, M.D., is supported by the NIH's National Institute of Allergy and Infectious Diseases (NIAID).

"Identification of this HIV-blocking factor opens new avenues for intervening in the early stage of HIV infection, before the virus can gain a toehold," says NIAID Director Anthony S. Fauci, M.D. "The discovery also gives us critical insights about viral uncoating, a little understood step in the viral lifecycle. Basic discoveries like this provide the scientific springboard to future improvements in therapies for HIV disease."

"Over the years," notes Dr. Sodroski, "we've learned quite a bit about how HIV enters cells. More recently, we've developed a picture of the late stages of the viral lifecycle, as it leaves the cell. However, the steps between virus entry and conversion of the viral RNA into DNA have been a black box." A key preparatory step is the removal, or uncoating, of the protective shell surrounding HIV's genetic material. This coat, called the capsid, must be removed before HIV can insert its genetic material into the host cell's DNA and begin to make copies of itself. (See http://www.niaid.nih.gov/newsroom/graphics/hiv1.jpg for a simplified diagram of HIV, including the capsid.)

The discovery of this host protein helps pry open the black box of uncoating. Called TRIM5-alpha, it is the first found to specifically target HIV's capsid. With the identification of a specific protein that powerfully inhibits viral uncoating, says Dr. Sodroski, comes the possibility of manipulating and enhancing its activity. For example, he notes, humans have a version of TRIM5-alpha. W
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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
25-Feb-2004


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