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Immunity. 2016 Jan 19;44(1):46-58. doi: 10.1016/j.immuni.2015.12.017.

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

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA.
2
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA.
4
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158-2140, USA.
5
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA; Division of Hematology and Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA.
6
Fundación Instituto Leloir-CONICET, Avenida Patricias Argentinas 435, Buenos Aires 1405, Argentina.
7
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA.
8
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA. Electronic address: ivan.marazzi@mssm.edu.

Erratum in

  • Immunity. 2016 Feb 16;44(2):438. Sachs, David H [corrected to Sachs, David].

Abstract

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.

PMID:
26789921
PMCID:
PMC4878455
DOI:
10.1016/j.immuni.2015.12.017
[Indexed for MEDLINE]
Free PMC Article

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