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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.
Heaton NS1, Moshkina N2, Fenouil R3, Gardner TJ1, Aguirre S1, Shah PS4, Zhao N2, Manganaro L1, Hultquist JF4, Noel J2, Sachs DH3, Hamilton J1, Leon PE1, Chawdury A5, Tripathi S1, Melegari C2, Campisi L2, Hai R1, Metreveli G2, Gamarnik AV6, Garc?a-Sastre A7, Greenbaum B5, Simon V2, Fernandez-Sesma A2, Krogan NJ4, Mulder LC2, van Bakel H3, Tortorella D1, Taunton J4, Palese P1, Marazzi I8.
Author information
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.
Copyright ? 2016 Elsevier Inc. All rights reserved.
PMID: 26789921 [PubMed - in process]
Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.
Heaton NS1, Moshkina N2, Fenouil R3, Gardner TJ1, Aguirre S1, Shah PS4, Zhao N2, Manganaro L1, Hultquist JF4, Noel J2, Sachs DH3, Hamilton J1, Leon PE1, Chawdury A5, Tripathi S1, Melegari C2, Campisi L2, Hai R1, Metreveli G2, Gamarnik AV6, Garc?a-Sastre A7, Greenbaum B5, Simon V2, Fernandez-Sesma A2, Krogan NJ4, Mulder LC2, van Bakel H3, Tortorella D1, Taunton J4, Palese P1, Marazzi I8.
Author information
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.
Copyright ? 2016 Elsevier Inc. All rights reserved.
PMID: 26789921 [PubMed - in process]