NS1 proteins of avian influenza A viruses can act as antagonists of the human alpha/beta interferon response.
Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-beta promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-beta induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-beta induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.
Hayman
A
A
School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom.
Comely
S
S
Lackenby
A
A
Hartgroves
L C S
LC
Goodbourn
S
S
McCauley
J W
JW
Barclay
W S
WS
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D007370:Interferon Type I; D017361:Viral Nonstructural Proteins