title: Dissecting the role of COPI complexes in influenza virus infection.
abstract: As an obligate pathogen, influenza virus requires host cell factors and compartments to mediate productive infection and to produce infectious progeny virus. Recently, several small interfering RNA (siRNA) knockdown screens revealed influenza virus host dependency proteins, all of which identified at least two subunits of the coat protein I (COPI) complex. COPI proteins oligomerize to form coated vesicles that transport contents between the Golgi apparatus and the endoplasmic reticulum, and they have also been reported to mediate endosomal trafficking. However, it remains unclear which steps in the influenza virus infection cycle rely on the COPI complex. Upon 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 specific decreases 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 play direct roles in viral membrane protein expression and assembly.
authors.affiliation: Program in Virology, Harvard Medical School, Cambridge, Massachusetts, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Sun
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhuang
mesh_terms: D045744:Cell Line, Tumor; D020755:Coat Protein Complex I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018699:Coated Vesicles / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D020755:Coat Protein Complex I; D034741:RNA, Small Interfering; D014763:Viral Matrix Proteins; D014764:Viral Proteins