title: siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection.
abstract: Little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. To uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based siRNA screen. We revealed an actin-remodeling pathway involving Rac1, PIP5K1- α, and Arp3, as essential for infection by pathogenic alphaviruses. Infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci. Actin foci are generated late in infection concomitantly with alphavirus envelope (E2) expression and are dependent on the activities of Rac1 and Arp3. E2 associates with actin in alphavirus-infected cells and co-localizes with Rac1-PIP5K1-α along actin filaments in the context of actin foci. Finally, Rac1, Arp3, and actin polymerization inhibitors interfere with E2 trafficking from the trans-Golgi network to the cell surface, suggesting a plausible model in which transport of E2 to the cell surface is mediated via Rac1- and Arp3-dependent actin remodeling.
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Sheli R
authors.initials: SR
authors.lastname: Radoshitzky
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pegoraro
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Xi Olì
authors.initials: XO
authors.lastname: Chī
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Lián
authors.initials: L
authors.lastname: D Ng
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Chiang
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Lucas
authors.initials: L
authors.lastname: Jozwick
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Jeremiah C
authors.initials: JC
authors.lastname: Clester
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Cooper
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Duane
authors.initials: D
authors.lastname: Courier
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: David P
authors.initials: DP
authors.lastname: Langan
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Knashka
authors.initials: K
authors.lastname: Underwood
authors.affiliation: Pathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Kuehl
authors.affiliation: Pathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Mei G
authors.initials: MG
authors.lastname: Sun
authors.affiliation: Integrated Research Facility at Fort Detrick (IRF-Frederick), Division of Clinical Research (DCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Yíngyún
authors.initials: Y
authors.lastname: Caì
authors.affiliation: Integrated Research Facility at Fort Detrick (IRF-Frederick), Division of Clinical Research (DCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Shu Qìng
authors.initials: SQ
authors.lastname: Yú
authors.affiliation: Integrated Research Facility at Fort Detrick (IRF-Frederick), Division of Clinical Research (DCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Robin
authors.initials: R
authors.lastname: Burk
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Rouzbeh
authors.initials: R
authors.lastname: Zamani
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kota
authors.affiliation: Integrated Research Facility at Fort Detrick (IRF-Frederick), Division of Clinical Research (DCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Fort Detrick, Frederick, Maryland, United States of America.
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, Maryland, United States of America.
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000199:Actins / Q000378:metabolism; D000524:Alphavirus / Q000235:genetics* / Q000378:metabolism; D018354:Alphavirus Infections / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D004261:DNA Replication / Q000235:genetics; D006801:Humans; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D034741:RNA, Small Interfering