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- , 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 20, 2016
- Accession Number
- AD1009283
Entities
People
- Chih-yuan Chiang
- Christopher L. Cooper
- David P. Langan
- Duane Courier
- Ginaluca Pegoraro
- Jens H. Kuhn
- Jeremiah C. Clester
- Kathleen A. Kuehl
- Knashka Underwood
- Krishna Kota
- Lian Dong
- Lucas Jozwick
- Mei G. Sun
- Robin Burk
- Rouzbeh Zamani
- Sheli R. Radoshitzky
- Shuiqing Yu
- Sina Bavari
- Xiaoli Chi
- Yíngyún Caì
Organizations
- United States Army Medical Research Institute of Infectious Diseases