The pericentriolar recycling endosome plays a key role in Vpu-mediated enhancement of HIV-1 particle release.
The HIV-1 accessory gene product Vpu is required for efficient viral particle release from infected human cells. The mechanism by which Vpu enhances particle assembly or release is not yet defined. Here, we identify an intracellular site that is critical for Vpu-mediated enhancement of particle release. Vpu was found to co-localize with markers for the pericentriolar recycling endosome. Expression of dominant negative mutants of Rab11a and myosin Vb that disrupt protein sorting through the recycling endosome abrogated the ability of Vpu to augment particle release. Remarkably, the effects of blocking recycling endosome function on HIV particle release were demonstrable only in human cell lines known to be responsive to Vpu, while no effect on particle release was seen in African green monkey cells. Inhibition of recycling endosome function in human cells also blocked the ability of HIV-2 envelope to enhance particle release. These studies indicate that Vpu and HIV-2 envelope glycoprotein enhance particle release via a common mechanism that requires the activity of the pericentriolar recycling endosome.
Varthakavi
Vasundhara
V
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2581, USA.
Smith
Rita M
RM
Martin
Kenneth L
KL
Derdowski
Aaron
A
Lapierre
Lynne A
LA
Goldenring
James R
JR
Spearman
Paul
P
D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins; D000086082:Viroporin Proteins
D054298:Human Immunodeficiency Virus Proteins; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D009218:Myosins; D054334:Viral Regulatory and Accessory Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C505832:MYO5B protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins