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Stuck on the membrane

The Journal of Cell Biology
The Rockefeller University Press
Publication Date
DOI: 10.1083/jcb.1803iti2
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JCB_1803iti.indd JCB • VOLUME 180 • NUMBER 3 • 2008444 Proteins gang up on HIV I t takes teamwork to de-feat HIV, as Campbell et al. reveal. The re- searchers show that clus- ters of defensive proteins inside cells capture viral invaders and promote their destruction. Defensive TRIM5 pro- teins have a narrow but important job: fending off retroviruses that normally attack other species. Human versions trap certain mouse viruses, for example, and those from rhesus monkeys take on HIV. The proteins seem to halt a retrovirus before it can recopy its RNA genome into DNA. But how TRIM5 proteins prevent infection remains unclear. In cells, the proteins form clusters known as cytoplasmic bodies. Campbell et al. investigated whether these clusters are important for stopping infection. The researchers followed HIV particles that invaded HeLa cells modifi ed to produce rhesus monkey TRIM5α. Cytoplasmic bodies and HIV particles cozied up, the team found. These asso- ciations were only detectable for a short time after the virus entered the cell. However, HIV remained stuck in the cytoplasmic bodies if the researchers added a drug that shuts down the proteasome— the cellular garbage disposal that chops up worn- out or damaged proteins. The team then observed interactions between labeled HIV particles and TRIM5α clusters in living cells. The viruses sometimes hooked onto an exist- ing cytoplasmic body and traveled along with it. Sometimes a virus broke away, but it had a coat of TRIM5α. And sometimes a new cytoplasmic body formed around a virus particle. The researchers conclude that shortly after viral entry, TRIM5α ensnares HIV particles and then collaborates with the proteasome to destroy them. The mechanism of destruction is obscure, since an individual virus is too large to fi t into the proteasome. But as several TRIM5α proteins that have latched onto an HIV particle get drawn into the proteasome, their pulling might tear the virus to pieces, “like

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