A protein has been identified in monkey cells that can block infection with HIV, according to US research published in the February 26th edition of Nature. Humans have a similar protein, called TRIM5-alpha, but it is less effective than the simian version at blocking infection with HIV. Nevertheless, investigators are speculating that the discovery could lead to the development of treatments that enhance the ability of TRIM5-alpha to block HIV. Alternatively, research could focus on developing a way of providing humans with the monkey version of the protein.
The discovery, made at the Dana-Farber Cancer Institute in the US, casts light on viral uncoating, a key but little-understood stage in the lifecycle of HIV. A vital step between the entry of HIV into a human cell and the conversion of its RNA into DNA is the removal, or uncoating, of the protective shell surrounding the virus’s genetic material. This coat, called the capsid, must be removed before HIV can insert its genetic material into a human cell and make copies of itself.
TRIM5-alpha is a blocking molecule, part of the immune system, and it specifically targets HIV’s capsid. Although the human version of TRIM5-alpha is not as effective as the monkey version in its anti-HIV effects, it does have some ability to block HIV, and investigators are speculating that it could help to explain why some people infected with HIV do not experience disease progression. TRIM5-alpha is one of a number of intracellular proteins with anti-HIV effects that may be expressed more or less strongly according to genetic inheritance.
It is not known exactly how TRIM5-alpha works, but investigators believe that the protein chops up HIV’s capsid, preventing the orderly uncoating the virus must undergo before it replicates.
Two possible therapeutic options have been opened up by the discovery. Research could focus on enhancing the ability of human TRIM5-alpha to block HIV. Another approach would be finding a way to use the more powerful monkey version of the protein in humans.
Prof Frances Gotch of Imperial College, London, who is a member of the NAM advisory panel told the BBC that the discovery was “very exciting” and could lead the way “to a prophylactic treatment which people at high risk might consider using”.
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Stremlau M et al. The cytoplasmic body component TRIM5-a restricts HIV-1 infection in Old World monkeys. Nature 427: 848 – 53, 2004.
Goff SP. HIV: replication trimmed back. Nature 427: 791 –92, 2004.