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J Virol. 2012 Dec 19. [Epub ahead of print]
Dissecting the role of COPI complexes on influenza virus infection.
Sun E, He J, Zhuang X.
Source
Program in Virology, Harvard Medical School.
Abstract
As an obligate pathogen, influenza virus requires host cell factors and compartments to mediate productive infection, and produce infectious progeny virus. Recently, several siRNA knockdown screens uncovered influenza host dependency proteins, of which all reports identified at least two subunits of the COPI complex. COPI proteins oligomerize to form coated vesicles that transport contents between the golgi apparatus and endoplasmic reticulum, and have previously been reported to also mediate endosomal trafficking. However, it remains unclear which of the steps in the influenza virus infection cycle rely on the COPI complex. Upon a systematic dissection of the influenza virus infection cycle- from entry to progeny virion production-we found that prolonged exposure to COPI complex disruption through siRNA depletion resulted in significant defects in virus internalization and trafficking to late endosomes. Acute inhibition of COPI complex recruitment to the golgi apparatus with pharmacological compounds failed to recapitulate the same entry defects as observed with the COPI-depleted cells, but did result in a specific decrease in viral membrane protein expression and assembly, leading to defects in progeny virion production. Taken together, our findings suggest that COPI complexes likely function indirectly in influenza virus entry, but do play a direct role in viral membrane protein expression and assembly.
PMID:
23255804
[PubMed - as supplied by publisher]
Dissecting the role of COPI complexes on influenza virus infection.
Sun E, He J, Zhuang X.
Source
Program in Virology, Harvard Medical School.
Abstract
As an obligate pathogen, influenza virus requires host cell factors and compartments to mediate productive infection, and produce infectious progeny virus. Recently, several siRNA knockdown screens uncovered influenza host dependency proteins, of which all reports identified at least two subunits of the COPI complex. COPI proteins oligomerize to form coated vesicles that transport contents between the golgi apparatus and endoplasmic reticulum, and have previously been reported to also mediate endosomal trafficking. However, it remains unclear which of the steps in the influenza virus infection cycle rely on the COPI complex. Upon a systematic dissection of the influenza virus infection cycle- from entry to progeny virion production-we found that prolonged exposure to COPI complex disruption through siRNA depletion resulted in significant defects in virus internalization and trafficking to late endosomes. Acute inhibition of COPI complex recruitment to the golgi apparatus with pharmacological compounds failed to recapitulate the same entry defects as observed with the COPI-depleted cells, but did result in a specific decrease in viral membrane protein expression and assembly, leading to defects in progeny virion production. Taken together, our findings suggest that COPI complexes likely function indirectly in influenza virus entry, but do play a direct role in viral membrane protein expression and assembly.
PMID:
23255804
[PubMed - as supplied by publisher]
