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

Publication ,  Journal Article
Heaton, NS; Moshkina, N; Fenouil, R; Gardner, TJ; Aguirre, S; Shah, PS; Zhao, N; Manganaro, L; Hultquist, JF; Noel, J; Sachs, D; Hamilton, J ...
Published in: Immunity
January 19, 2016

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.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

January 19, 2016

Volume

44

Issue

1

Start / End Page

46 / 58

Location

United States

Related Subject Headings

  • Virus Replication
  • Proteomics
  • Protein Folding
  • Models, Theoretical
  • Mass Spectrometry
  • Influenza A virus
  • Immunoprecipitation
  • Immunology
  • Humans
  • Host-Parasite Interactions
 

Citation

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Heaton, N. S., Moshkina, N., Fenouil, R., Gardner, T. J., Aguirre, S., Shah, P. S., … Marazzi, I. (2016). Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection. Immunity, 44(1), 46–58. https://doi.org/10.1016/j.immuni.2015.12.017
Heaton, Nicholas S., Natasha Moshkina, Romain Fenouil, Thomas J. Gardner, Sebastian Aguirre, Priya S. Shah, Nan Zhao, et al. “Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.Immunity 44, no. 1 (January 19, 2016): 46–58. https://doi.org/10.1016/j.immuni.2015.12.017.
Heaton NS, Moshkina N, Fenouil R, Gardner TJ, Aguirre S, Shah PS, et al. Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection. Immunity. 2016 Jan 19;44(1):46–58.
Heaton, Nicholas S., et al. “Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.Immunity, vol. 44, no. 1, Jan. 2016, pp. 46–58. Pubmed, doi:10.1016/j.immuni.2015.12.017.
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. Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection. Immunity. 2016 Jan 19;44(1):46–58.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

January 19, 2016

Volume

44

Issue

1

Start / End Page

46 / 58

Location

United States

Related Subject Headings

  • Virus Replication
  • Proteomics
  • Protein Folding
  • Models, Theoretical
  • Mass Spectrometry
  • Influenza A virus
  • Immunoprecipitation
  • Immunology
  • Humans
  • Host-Parasite Interactions