Named TRIM5-alpha, the blocking molecule may be the first example of an innate, previously unknown arm of the immune system that patrols the body for viruses and, if they enter a cell, prevents them from causing harm.
"This is the first glimpse of a form of intracellular immunity made up of natural factors that specifically and potently block retroviruses such as HIV-1," says Joseph Sodroski, MD, senior author of a paper appearing in this week's issue of Nature. The lead author is Matthew Stremlau, a Harvard Medical School graduate student. "Our finding expands our vision of what we might be able to manipulate to block the very early stages of HIV-1 infection," Sodroski says.
Human cells contain a similar TRIM5-alpha protein but it is less effective than the monkey version in blocking HIV-1 infection. It's possible that the potency of TRIM5-alpha differs among individuals because of genetic variations, which may explain why some people infected with HIV progress rapidly to AIDS, while others have remained healthy for decades.
While therapeutic use of the finding remains speculative, says Sodroski, researchers might find ways to increase effectiveness of the human TRIM5-alpha molecule, or, conceivably, administer the more potent monkey version as a therapy.
TRIM5-alpha proteins reside in "cytoplasmic bodies" inside HIV-1 target cells. The discovery begins to shed light on how the virus, once it has breached the cell membrane, uncoats and converts its genetic material, RNA, into DNA for replication. In a key step in the process, the inner core of the virus sheds its capsid
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
25-Feb-2004