siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection

作者：Sheli R. Radoshitzky, Gianluca Pegoraro, Xiǎolì Chī, Lián Dŏng, Chih-Yuan Chiang, Jozwick Lucas, Jeremiah C. Clester, Christopher L. Cooper, Duane Courier, David Langan, K. Dante Underwood, Kathleen Kuehl, Mei Sun, Yíngyún Caì, Shuǐqìng Yú, Robin Burk, Rouzbeh Zamani, Krishna P. Kota, Jens H. Kuhn, Sina Bavari · 发表于：PLoS Pathogens · 年份：2016 · DOI：10.1371/journal.ppat.1005466 · 被引用次数：40 · 研究领域：Viral Infections and Outbreaks Research、Cytomegalovirus and herpesvirus research、Virology and Viral Diseases

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.