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The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production.

Alroy I, Tuvia S, Greener T, Gordon D, Barr HM, Taglicht D, Mandil-Levin R, Ben-Avraham D, Konforty D, Nir A, Levius O, Bicoviski V, Dori M, Cohen S, Yaar L, Erez O, Propheta-Meiran O, Koskas M, Caspi-Bachar E, Alchanati I, Sela-Brown A, Moskowitz H, Tessmer U, Schubert U, Reiss Y

Proteologics Ltd., 2 Holzman Street, Rehovot Science Park, Rehovot 76124, Israel.

HIV type 1 (HIV-1) was shown to assemble either at the plasma membrane or in the membrane of late endosomes. Now, we report an essential role for human ubiquitin ligase POSH (Plenty of SH3s; hPOSH), a trans-Golgi network-associated protein, in the targeting of HIV-1 to the plasma membrane. Small inhibitory RNA-mediated silencing of hPOSH ablates virus secretion and Gag plasma membrane localization. Reintroduction of native, but not a RING finger mutant, hPOSH restores virus release and Gag plasma membrane localization in hPOSH-depleted cells. Furthermore, expression of the RING finger mutant hPOSH inhibits virus release and induces accumulation of intracellular Gag in normal cells. Together, our results identify a previously undescribed step in HIV biogenesis and suggest a direct function for hPOSH-mediated ubiquitination in protein sorting at the trans-Golgi network. Consequently, hPOSH may be a useful host target for therapeutic intervention.

Published 2 February 2005 in Proc Natl Acad Sci U S A, 102(5): 1478-83.
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