Truncation of the NS1 protein converts a low pathogenic avian influenza virus into a strong interferon inducer in duck cells

Avian Dis. 2010 Mar;54(1 Suppl):527-31. doi: 10.1637/8707-031709-Reg.1.

Abstract

The NS1 protein of influenza A viruses is known as a nonessential virulence factor inhibiting type I interferon (IFN) production in mammals and in chicken cells. Whether NS1 inhibits the induction of type I IFNs in duck cells is currently unknown. In order to investigate this issue, we used reverse genetics to generate a virus expressing a truncated NS1 protein. Using the low pathogenic avian influenza virus A/turkey/Italy/977/1999 (H7N1) as a backbone, we were able to rescue a virus expressing a truncated NS1 protein of 99 amino acids in length. The truncated virus replicated poorly in duck embryonic fibroblasts, but reached high titers in the mammalian IFN-deficient Vero cell line. Using a gene reporter system to measure duck type I IFN production, we showed that the truncated virus is a potent inducer of type I IFN in cell culture. These results show that the NS1 protein functions to prevent the induction of IFN in duck cells and underline the need for a functional NS1 protein in order for the virus to express its full virulence.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Ducks* / embryology
  • Fibroblasts
  • Gene Expression Regulation, Viral
  • Humans
  • Influenza A virus / classification
  • Influenza A virus / genetics
  • Influenza A virus / pathogenicity*
  • Interferons / genetics
  • Interferons / metabolism*
  • Mutation
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / genetics*
  • Virus Replication

Substances

  • INS1 protein, influenza virus
  • Viral Nonstructural Proteins
  • Interferons