tetano
Editor, Senior Moderator
Immunity. 2016 Jan 19;44(1):46-58. doi: 10.1016/j.immuni.2015.12.017.
[h=1]Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.[/h] Heaton NS[SUP]1[/SUP], Moshkina N[SUP]2[/SUP], Fenouil R[SUP]3[/SUP], Gardner TJ[SUP]1[/SUP], Aguirre S[SUP]1[/SUP], Shah PS[SUP]4[/SUP], Zhao N[SUP]2[/SUP], Manganaro L[SUP]1[/SUP], Hultquist JF[SUP]4[/SUP], Noel J[SUP]2[/SUP], Sachs DH[SUP]3[/SUP], Hamilton J[SUP]1[/SUP], Leon PE[SUP]1[/SUP], Chawdury A[SUP]5[/SUP], Tripathi S[SUP]1[/SUP], Melegari C[SUP]2[/SUP], Campisi L[SUP]2[/SUP], Hai R[SUP]1[/SUP], Metreveli G[SUP]2[/SUP], Gamarnik AV[SUP]6[/SUP], Garc?a-Sastre A[SUP]7[/SUP], Greenbaum B[SUP]5[/SUP], Simon V[SUP]2[/SUP], Fernandez-Sesma A[SUP]2[/SUP], Krogan NJ[SUP]4[/SUP], Mulder LC[SUP]2[/SUP], van Bakel H[SUP]3[/SUP], Tortorella D[SUP]1[/SUP], Taunton J[SUP]4[/SUP], Palese P[SUP]1[/SUP], Marazzi I[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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]
[h=1]Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.[/h] Heaton NS[SUP]1[/SUP], Moshkina N[SUP]2[/SUP], Fenouil R[SUP]3[/SUP], Gardner TJ[SUP]1[/SUP], Aguirre S[SUP]1[/SUP], Shah PS[SUP]4[/SUP], Zhao N[SUP]2[/SUP], Manganaro L[SUP]1[/SUP], Hultquist JF[SUP]4[/SUP], Noel J[SUP]2[/SUP], Sachs DH[SUP]3[/SUP], Hamilton J[SUP]1[/SUP], Leon PE[SUP]1[/SUP], Chawdury A[SUP]5[/SUP], Tripathi S[SUP]1[/SUP], Melegari C[SUP]2[/SUP], Campisi L[SUP]2[/SUP], Hai R[SUP]1[/SUP], Metreveli G[SUP]2[/SUP], Gamarnik AV[SUP]6[/SUP], Garc?a-Sastre A[SUP]7[/SUP], Greenbaum B[SUP]5[/SUP], Simon V[SUP]2[/SUP], Fernandez-Sesma A[SUP]2[/SUP], Krogan NJ[SUP]4[/SUP], Mulder LC[SUP]2[/SUP], van Bakel H[SUP]3[/SUP], Tortorella D[SUP]1[/SUP], Taunton J[SUP]4[/SUP], Palese P[SUP]1[/SUP], Marazzi I[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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]