Inhibition of host innate immune responses and pathogenicity of recombinant Newcastle disease viruses expressing NS1 genes of influenza A viruses.
The NS1 protein has been associated with the virulence of influenza A viruses. To evaluate the role of the NS1 protein in pathogenicity of pandemic H5N1 avian influenza and H1N1 2009 influenza viruses, recombinant Newcastle disease viruses (rNDVs) expressing NS1 proteins were generated. Expression of the NS1 proteins resulted in inhibition of host innate immune responses (beta interferon and protein kinase R production). In addition, the NS1 proteins were localized predominantly in the nucleus of virus-infected cells. Consequently, expression of the NS1 protein contributed to an increase in pathogenicity of rNDV in chickens. In particular, mutational analysis of H5N1 NS1 protein indicated that both the RNA-binding and effector domains affect virus pathogenicity synergistically. Our study also demonstrated that expression of H1N1/09 NS1 resulted in enhanced replication of rNDV in human cells, indicating that function of the NS1 proteins can be host-species-specific.
Kim
Shin-Hee
SH
Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA.
Samal
Siba K
SK
Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA.
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002642:Chick Embryo; D002645:Chickens; D006801:Humans; D007108:Immune Tolerance; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000472:pathogenicity; D016899:Interferon-beta / Q000037:antagonists & inhibitors; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D011995:Recombination, Genetic; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors
C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors; D016899:Interferon-beta; D019892:eIF-2 Kinase