Truncation of the NS1 protein converts a low pathogenic avian influenza virus into a strong interferon inducer in duck cells.
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.
Soubies
Sébastien Mathieu
SM
INRA, UMR 1225, Interactions Hôtes Agents Pathogenes, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
Volmer
Christelle
C
Guérin
Jean-Luc
JL
Volmer
Romain
R
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004372:Ducks / Q000196:embryology; D005347:Fibroblasts; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D007372:Interferons