Genome-wide RNAi screen identifies novel host proteins required for alphavirus entry
Autor(es): Ooi Yaw Shin, Stiles Katie M, Liu Catherine Y, Taylor Gwen M, Kielian Margaret
Resumo: The enveloped alphaviruses include important - emerging human pathogens such as Chikungunya virus - Eastern equine encephalitis virus. Alphaviruses enter cells by clathrin-mediated endocytosis, - exit by budding from the plasma membrane. While there has been considerable progress in defining the structure - function of the viral proteins, relatively little is known about the host factors involved in alphavirus infection. We used a genome-wide siRNA screen to identify host factors that promote or inhibit alphavirus infection in human cells. Fuzzy homologue (FUZ), a protein with reported roles in planar cell polarity - cilia biogenesis, was required for the clathrin-dependent internalization of both alphaviruses - the classical endocytic lig- transferrin. The tetraspanin membrane protein TSPAN9 was critical for the efficient fusion of low pH-triggered virus with the endosome membrane. FUZ - TSPAN9 were broadly required for infection by the alphaviruses Sindbis virus, Semliki Forest virus, - Chikungunya virus, but were not required by the structurally-related flavivirus Dengue virus. Our results highlight the unanticipated functions of FUZ - TSPAN9 in distinct steps of alphavirus entry - suggest novel host proteins that may serve as targets for antiviral therapy.
Imprenta: PLoS Pathogens, v. 9, n. 12, p. e1003835, 2013
Identificador do objeto digital: 10.1371/journal.ppat.1003835
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Genome ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Dengue
Data de publicação: 2013
