GGA and Arf proteins modulate retrovirus assembly and release.
The Gag protein is the major structural determinant of retrovirus assembly. Although a number of cellular factors have been reported to facilitate retrovirus release, little is known about the cellular machinery that directs Gag to the site of virus assembly. Here, we report roles for the Golgi-localized gamma-ear containing Arf-binding (GGA) and ADP ribosylation factor (Arf) proteins in retrovirus particle assembly and release. Whereas siRNA-mediated depletion of GGA2 and GGA3 led to a significant increase in particle release in a late domain-dependent manner, GGA overexpression severely reduced retrovirus particle production by impairing Gag trafficking to the membrane. GGA overexpression inhibited retroviral assembly and release by disrupting Arf protein activity. Furthermore, disruption of endogenous Arf activity inhibited particle production by decreasing Gag-membrane binding. These findings identify the GGA proteins as modulators of HIV-1 release and the Arf proteins as critical cellular cofactors in retroviral Gag trafficking to the plasma membrane.
Joshi
Anjali
A
Virus-Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702-1201, USA.
Garg
Himanshu
H
Nagashima
Kunio
K
Bonifacino
Juan S
JS
Freed
Eric O
EO
D020727:ADP-Ribosylation Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014771:Virion / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014775:Virus Activation; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; C407306:GGA adaptor proteins; D034741:RNA, Small Interfering; D054301:gag Gene Products, Human Immunodeficiency Virus; D020727:ADP-Ribosylation Factors