Influenza virus-host interactome screen as a platform for antiviral drug development.
Cell Host Microbe
; 16(6): 795-805, 2014 Dec 10.
Article
en En
| MEDLINE
| ID: mdl-25464832
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Orthomyxoviridae
/
Proteínas Virales
/
Mapeo de Interacción de Proteínas
/
Gripe Humana
/
Mapas de Interacción de Proteínas
Tipo de estudio:
Evaluation_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Host Microbe
Asunto de la revista:
MICROBIOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos