J Virol. 2012 Dec 19. [Epub ahead of print]
Contribution of dsRNA and CPSF30 Binding Domains of Influenza Virus NS1 to the Inhibition of Type I IFN Production and Activation of Human Dendritic Cells.
Ramos I, Carnero E, Bernal-Rubio D, Seibert CW, Westera L, Garc?a-Sastre A, Fernandez-Sesma A.
Source
Department of Microbiology.
Abstract
The influenza virus NS1 protein inhibits innate immunity by multiple mechanisms. We previously reported that NS1 is able to inhibit the production of type I IFN and the production of pro-inflammatory cytokines in human primary dendritic cells (DCs). Here, we used recombinant viruses expressing mutant NS1 from A/Texas/36/91 and A/Puerto Rico/08/34 strains in order to analyze the contribution of different NS1 domains to its antagonist functions. We show that the CPSF30 binding function of the NS1 protein from A/Texas/36/91 influenza virus, which is absent in the A/Puerto Rico/08/34 strain, is essential for counteracting these innate immune events in DCs. However, the dsRNA binding domain, present in both strains, specifically inhibits induction of type I IFN genes in infected DCs. While it is only essential for inhibition of type I IFN proteins and pro-inflammatory cytokine production in cells infected with influenza viruses lacking a functional CPSF30 binding domain, such as A/Puerto Rico/08/34.
PMID:
23255794
[PubMed - as supplied by publisher]
Contribution of dsRNA and CPSF30 Binding Domains of Influenza Virus NS1 to the Inhibition of Type I IFN Production and Activation of Human Dendritic Cells.
Ramos I, Carnero E, Bernal-Rubio D, Seibert CW, Westera L, Garc?a-Sastre A, Fernandez-Sesma A.
Source
Department of Microbiology.
Abstract
The influenza virus NS1 protein inhibits innate immunity by multiple mechanisms. We previously reported that NS1 is able to inhibit the production of type I IFN and the production of pro-inflammatory cytokines in human primary dendritic cells (DCs). Here, we used recombinant viruses expressing mutant NS1 from A/Texas/36/91 and A/Puerto Rico/08/34 strains in order to analyze the contribution of different NS1 domains to its antagonist functions. We show that the CPSF30 binding function of the NS1 protein from A/Texas/36/91 influenza virus, which is absent in the A/Puerto Rico/08/34 strain, is essential for counteracting these innate immune events in DCs. However, the dsRNA binding domain, present in both strains, specifically inhibits induction of type I IFN genes in infected DCs. While it is only essential for inhibition of type I IFN proteins and pro-inflammatory cytokine production in cells infected with influenza viruses lacking a functional CPSF30 binding domain, such as A/Puerto Rico/08/34.
PMID:
23255794
[PubMed - as supplied by publisher]