The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production.
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.
Alroy
Iris
I
Proteologics Ltd., 2 Holzman Street, Rehovot Science Park, Rehovot 76124, Israel.
Tuvia
Shmuel
S
Greener
Tsvika
T
Gordon
Daphna
D
Barr
Haim M
HM
Taglicht
Daniel
D
Mandil-Levin
Revital
R
Ben-Avraham
Danny
D
Konforty
Dalit
D
Nir
Anat
A
Levius
Orit
O
Bicoviski
Vivian
V
Dori
Mally
M
Cohen
Shenhav
S
Yaar
Liora
L
Erez
Omri
O
Propheta-Meiran
Oshrat
O
Koskas
Mordechai
M
Caspi-Bachar
Elanite
E
Alchanati
Iris
I
Sela-Brown
Alin
A
Moskowitz
Haim
H
Tessmer
Uwe
U
Schubert
Ulrich
U
Reiss
Yuval
Y
D002462:Cell Membrane / Q000201:enzymology / Q000821:virology; D003001:Cloning, Molecular; D015683:Gene Products, gag / Q000378:metabolism; D020868:Gene Silencing; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D021601:trans-Golgi Network / Q000201:enzymology*
D015683:Gene Products, gag; D011994:Recombinant Proteins; C498193:SH3RF1 protein, human; D044767:Ubiquitin-Protein Ligases