tetano
Editor, Senior Moderator
Cell Host Microbe. 2014 Nov 20. pii: S1931-3128(14)00398-9. doi: 10.1016/j.chom.2014.11.002. [Epub ahead of print]
Influenza Virus-Host Interactome Screen as a Platform for Antiviral Drug Development.
Watanabe T1, Kawakami E2, Shoemaker JE1, Lopes TJ2, Matsuoka Y3, Tomita Y2, Kozuka-Hata H4, Gorai T5, Kuwahara T6, Takeda E6, Nagata A6, Takano R6, Kiso M6, Yamashita M6, Sakai-Tagawa Y6, Katsura H6, Nonaka N6, Fujii H6, Fujii K2, Sugita Y6, Noda T6, Goto H6, Fukuyama S1, Watanabe S7, Neumann G8, Oyama M4, Kitano H9, Kawaoka Y10.
Author information
Abstract
Host factors required for viral replication are ideal drug targets because they are less likely than viral proteins to mutate under drug-mediated selective pressure. Although genome-wide screens have identified host proteins involved in influenza virus replication, limited mechanistic understanding of how these factors affect influenza has hindered potential drug development. We conducted a systematic analysis to identify and validate host factors that associate with influenza virus proteins and affect viral replication. After identifying over 1,000 host factors that coimmunoprecipitate with specific viral proteins, we generated a network of virus-host protein interactions based on the stage of the viral life cycle affected upon host factor downregulation. Using compounds that inhibit these host factors, we validated several proteins, notably Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) and JAK1, as potential antiviral drug targets. Thus, virus-host interactome screens are powerful strategies to identify targetable host factors and guide antiviral drug development.
Copyright ? 2014 Elsevier Inc. All rights reserved.
PMID:
25464832
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25464832
Influenza Virus-Host Interactome Screen as a Platform for Antiviral Drug Development.
Watanabe T1, Kawakami E2, Shoemaker JE1, Lopes TJ2, Matsuoka Y3, Tomita Y2, Kozuka-Hata H4, Gorai T5, Kuwahara T6, Takeda E6, Nagata A6, Takano R6, Kiso M6, Yamashita M6, Sakai-Tagawa Y6, Katsura H6, Nonaka N6, Fujii H6, Fujii K2, Sugita Y6, Noda T6, Goto H6, Fukuyama S1, Watanabe S7, Neumann G8, Oyama M4, Kitano H9, Kawaoka Y10.
Author information
Abstract
Host factors required for viral replication are ideal drug targets because they are less likely than viral proteins to mutate under drug-mediated selective pressure. Although genome-wide screens have identified host proteins involved in influenza virus replication, limited mechanistic understanding of how these factors affect influenza has hindered potential drug development. We conducted a systematic analysis to identify and validate host factors that associate with influenza virus proteins and affect viral replication. After identifying over 1,000 host factors that coimmunoprecipitate with specific viral proteins, we generated a network of virus-host protein interactions based on the stage of the viral life cycle affected upon host factor downregulation. Using compounds that inhibit these host factors, we validated several proteins, notably Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) and JAK1, as potential antiviral drug targets. Thus, virus-host interactome screens are powerful strategies to identify targetable host factors and guide antiviral drug development.
Copyright ? 2014 Elsevier Inc. All rights reserved.
PMID:
25464832
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25464832