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Detection of Viral RNA by Fluorescence in situ Hybridization (FISH)
Published on: May 5, 2012
GGA and Arf proteins modulate retrovirus assembly and release
Anjali Joshi1, Himanshu Garg, Kunio Nagashima
1Virus-Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702-1201, USA.
Molecular Cell
|April 29, 2008
Summary
Golgi-localized gamma-ear containing Arf-binding (GGA) proteins and ADP ribosylation factor (Arf) proteins are key cellular factors in retrovirus assembly. GGA proteins modulate HIV-1 release by regulating Gag trafficking to the plasma membrane.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- The Gag protein is essential for retrovirus assembly and release.
- Cellular machinery directing Gag to assembly sites remains largely unknown.
- Golgi-associated proteins are implicated in viral particle formation.
Purpose of the Study:
- To investigate the role of Golgi-localized gamma-ear containing Arf-binding (GGA) and ADP ribosylation factor (Arf) proteins in retrovirus assembly and release.
- To elucidate the mechanism by which GGA and Arf proteins influence Gag protein trafficking and viral particle production.
Main Methods:
- Small interfering RNA (siRNA)-mediated gene silencing to deplete GGA2 and GGA3.
- Overexpression of GGA proteins to assess their impact on retrovirus production.
- Disruption of endogenous Arf protein activity.
- Analysis of Gag protein trafficking to the cell membrane.
Main Results:
- Depletion of GGA2 and GGA3 increased retrovirus particle release in a late domain-dependent manner.
- Overexpression of GGA proteins reduced retrovirus particle production by impairing Gag trafficking to the membrane.
- GGA overexpression disrupted Arf protein activity, inhibiting retroviral assembly and release.
- Disruption of Arf activity decreased Gag-membrane binding, inhibiting particle production.
Conclusions:
- GGA proteins act as modulators of HIV-1 release.
- Arf proteins are critical cellular cofactors in the trafficking of retroviral Gag to the plasma membrane.
- The GGA-Arf pathway is a significant regulator of retroviral assembly and release.
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