Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.

Published

Journal Article

Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.

Full Text

Duke Authors

Cited Authors

  • Heaton, NS; Moshkina, N; Fenouil, R; Gardner, TJ; Aguirre, S; Shah, PS; Zhao, N; Manganaro, L; Hultquist, JF; Noel, J; Sachs, D; Hamilton, J; Leon, PE; Chawdury, A; Tripathi, S; Melegari, C; Campisi, L; Hai, R; Metreveli, G; Gamarnik, AV; García-Sastre, A; Greenbaum, B; Simon, V; Fernandez-Sesma, A; Krogan, NJ; Mulder, LCF; van Bakel, H; Tortorella, D; Taunton, J; Palese, P; Marazzi, I

Published Date

  • January 2016

Published In

Volume / Issue

  • 44 / 1

Start / End Page

  • 46 - 58

PubMed ID

  • 26789921

Pubmed Central ID

  • 26789921

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2015.12.017

Language

  • eng