Accession Number : AD1009283


Title :   siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection


Descriptive Note : Journal Article


Corporate Author : USAMRIID Frederick United States


Personal Author(s) : Radoshitzky,Sheli R ; Bavari,Sina ; Pegoraro,Ginaluca ; Chi,Xiaoli ; Dong,Lian ; Chiang,Chih-Yuan ; Jozwick,Lucas ; Clester,Jeremiah C ; Cooper,Christopher L ; Courier,Duane ; Langan,David P ; Underwood,Knashka ; Kuehl,Kathleen A ; Sun,Mei G ; Cai,Yingyun ; Yu,Shuiqing ; Burk,Robin ; Zamani,Rouzbeh ; Kota,Krishna ; Kuhn,Jens H


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1009283.pdf


Report Date : 20 May 2016


Pagination or Media Count : 131


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- , andArp3, 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- 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- andArp3-dependent actin remodeling.


Descriptors :   equine encephalitis , togaviridae , Chikungunya virus , ribonucleic acids , medical screening , assaying , membranes


Distribution Statement : APPROVED FOR PUBLIC RELEASE