HIV-1 is unable to replicate in Old World monkeys, even though it can enter their cells. In 2004, Joseph Sodroski at Dana-Farber Cancer Institute in Boston and his colleagues identified the factor responsible. They transduced human cells with a complementary DNA (cDNA) library prepared from rhesus monkeys. Resistant cells commonly harbored cDNA for the cytoplasmic body component TRIM5α. The research revealed an intracellular immunity mechanism to viruses "we didn't realize existed before," Sodroski says. TRIM5α possesses at its C-terminal end a domain with variable regions on it "similar to immunoglobulin," he adds.
The identity of a factor in primates that blocked HIV-1, "was the hottest topic of its time in the retrovirus field," recalls Stephen Goff at Columbia University in New York. Much work has since gone into how it works. "We've found TRIM5 recognizes viral capsids in a fairly specific way," Sodroski says. "We believe...
Sodroski adds that although TRIM5 hasn't been found outside of primates, more mammalian antiviral TRIM proteins are on the horizon. "We recently reported a TRIM protein with antiretroviral activity from the same family as TRIM5, but found so far only in hoofed animals."
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