Mysterious Monkey Molecule Keeps HIV at Bay
TRIM Protein Stops AIDS Virus, Promises Entirely New Treatment
Feb. 25, 2004 -- A mysterious monkey protein protects animals from HIV. The finding gives hope there could be entirely new ways to treat HIV and AIDS.
Why don't most monkeys get AIDS from HIV? It's one of the great puzzles of AIDS research. Now the missing piece to this puzzle is in hand, report researchers from Boston's Dana-Farber Cancer Institute. And once the puzzle is put together, it may very well be the key to new AIDS treatments.
Joseph Sodroski, MD, led a research team that cleverly used the latest techniques in genetic engineering to find the gene that protects rhesus monkeys from the human AIDS virus. That gene encodes a protein -- TRIM5-alpha -- that lurks within cells in mysterious structures known as cytoplasmic bodies.
Nobody knows what cytoplasmic bodies are there for -- much less exactly what TRIM molecules are supposed to do. But Sodroski's team offers proof that TRIM5-alpha does something to HIV that nothing else can do: It keeps HIV from unzipping its deadly bag of tricks.
"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," Sodroski says in a news release. "Our finding expands our vision of what we might be able to manipulate to block the very early stages of HIV-1 infection."
The Evolution of a "New" AIDS Treatment
The AIDS virus is a retrovirus. Retroviruses have been around ever since monkeys evolved. To survive, monkeys evolved natural ways to fight retrovirus infection. TRIM5-alpha appears to be one of the most effective of these natural retrovirus-fighting weapons.
Like monkeys, humans have a form of TRIM5-alpha. It does have some anti-HIV activity -- which may help explain why a few people don't get AIDS even after many years of HIV infection. But HIV jumped to humans from chimpanzees -- bypassing our natural antiretroviral defenses.
Nevertheless, the new findings offer insight helpful in finding new AIDS treatments:
- A form of TRIM5-alpha might be helpful as an AIDS drug, or it might point the way to new kinds of AIDS treatments.
- Researchers may find a way to make human TRIM5-alpha more potent against HIV.
- By knocking out TRIM5-alpha in monkeys, researchers could develop better models of HIV disease for learning more about HIV -- and for testing new AIDS drugs much more quickly.
Once HIV enters a cell, it unzips its outer coat and gets to work. This unzipping has to be done just so -- and TRIM5-alpha throws a monkey wrench into this process. Not much is known about this stage of the HIV life cycle. The Sodroski team's findings are shedding light on this crucial target for new AIDS treatments. Their report appears in the Feb. 26 issue of Nature.