tetano
Editor, Senior Moderator
J Virol. 2013 Dec 11. [Epub ahead of print]
PB2 588I enhances the 2009 H1N1 pandemic influenza virus virulence by increasing viral replication and exacerbating PB2 inhibition of interferon-beta expression.
Zhao Z, Yi C, Zhao L, Wang S, Zhou L, Hu Y, Zou W, Chen H, Jin M.
Author information
Abstract
The 2009 pandemic H1N1 influenza virus (pdm/09) is typically mildly virulent in mice. In a previous study, we identified four novel swine isolates of pdm/09 viruses that exhibited high lethality in mice. Comparing the consensus sequences of the PB2 subunit of human isolates of pdm/09 viruses with those of the four swine isolate viruses exhibited one consensus mutation: T588I. In this study, we determined that 588T is an amino acid mutation conserved in pdm/09 viruses that was exceedingly rare in previous human influenza isolates. To investigate whether the PB2-T558I mutation has an effect on the increased pathogenicity, we rescued a variant containing PB2-588I (Mex_PB2-588I) in the pdm/09 virus, A/Mexico/4486/2009(H1N1), referred to Mex_WT, and characterized the variant in vitro and in vivo. The results indicated that the mutation significantly enhanced polymerase activity in mammalian cells, and the variant exhibited increased growth properties and induced significant weight loss in a mouse model compared to the wild type (WT). We determined that the mutation exacerbated PB2 inhibition of MAVS-mediated IFN-β expression, and PB2-588I was observed to bind to MAVS more efficiently than PB2-588T. The variant induced lower levels of host IFN-β expression than the WT strain during infection. These findings indicate that the pdm/09 influenza virus has increased pathogenicity upon the acquisition of the PB2-T588I mutation and highlight the need for the continued surveillance of the genetic variation of molecular markers in influenza viruses, because of their potential effects on pathogenicity and threats to human health.
PMID:
24335306
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24335306
PB2 588I enhances the 2009 H1N1 pandemic influenza virus virulence by increasing viral replication and exacerbating PB2 inhibition of interferon-beta expression.
Zhao Z, Yi C, Zhao L, Wang S, Zhou L, Hu Y, Zou W, Chen H, Jin M.
Author information
Abstract
The 2009 pandemic H1N1 influenza virus (pdm/09) is typically mildly virulent in mice. In a previous study, we identified four novel swine isolates of pdm/09 viruses that exhibited high lethality in mice. Comparing the consensus sequences of the PB2 subunit of human isolates of pdm/09 viruses with those of the four swine isolate viruses exhibited one consensus mutation: T588I. In this study, we determined that 588T is an amino acid mutation conserved in pdm/09 viruses that was exceedingly rare in previous human influenza isolates. To investigate whether the PB2-T558I mutation has an effect on the increased pathogenicity, we rescued a variant containing PB2-588I (Mex_PB2-588I) in the pdm/09 virus, A/Mexico/4486/2009(H1N1), referred to Mex_WT, and characterized the variant in vitro and in vivo. The results indicated that the mutation significantly enhanced polymerase activity in mammalian cells, and the variant exhibited increased growth properties and induced significant weight loss in a mouse model compared to the wild type (WT). We determined that the mutation exacerbated PB2 inhibition of MAVS-mediated IFN-β expression, and PB2-588I was observed to bind to MAVS more efficiently than PB2-588T. The variant induced lower levels of host IFN-β expression than the WT strain during infection. These findings indicate that the pdm/09 influenza virus has increased pathogenicity upon the acquisition of the PB2-T588I mutation and highlight the need for the continued surveillance of the genetic variation of molecular markers in influenza viruses, because of their potential effects on pathogenicity and threats to human health.
PMID:
24335306
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24335306