The B allele of the NS gene of avian influenza viruses, but not the A allele, attenuates a human influenza A virus for squirrel monkeys.
The nonstructural (NS) genes of avian influenza A viruses have been divided into two groups on the basis of nucleotide sequence homology, which we have referred to here as alleles A and B. We sequenced the NS genes of eight additional avian influenza A viruses in order to define the differences between these two alleles more thoroughly. Four of the viruses had NS gene sequences which resembled that of A/FPV/Rostock/34 and belonged to allele A while the other four viruses had NS gene sequences more similar to that of A/Duck/Alberta/76 and belonged to allele B. There was approximately 90% sequence homology within alleles and 72% homology between alleles. As previously reported the NS genes of human influenza A viruses belong to allele A. We constructed single gene avian-human reassortant influenza A viruses containing an allele A or B NS gene segment from an avian influenza A virus and all other genes from a human influenza A virus and tested these reassortants for their ability to grow in the respiratory tract of a nonhuman primate. Reassortants containing an avian NS gene segment of allele B were significantly restricted in growth in the respiratory tract of squirrel monkeys while reassortants with an allele A NS gene segment were not. The divergent evolution of the B NS allele in birds may have resulted in gene products which do not function optimally in cooperation with genes from a human virus in viral replication in primate respiratory epithelium.
Treanor
J J
JJ
Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Snyder
M H
MH
London
W T
WT
Murphy
B R
BR
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002213:Capsid / Q000235:genetics*; D005814:Genes, Viral; D009980:Influenza A virus / Q000235:genetics* / Q000254:growth & development*; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000382:microbiology; D012453:Saimiri / Q000382:microbiology; D012689:Sequence Homology, Nucleic Acid; D014132:Trachea / Q000382:microbiology; D014758:Viral Core Proteins / Q000235:genetics*; D017361:Viral Nonstructural Proteins; D014779:Virus Replication
D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins