Virulence-associated sequence duplication at the hemagglutinin cleavage site of avian influenza viruses

Virus Res. 1997 Jun;49(2):173-86. doi: 10.1016/s0168-1702(97)01468-8.


Recent highly pathogenic (HP) field isolates of avian influenza (AI) virus from Mexico all possess an insertion of at least two basic amino acids (arg-lys) at the cleavage site of the hemagglutinin (HA) glycoprotein. One HP isolate has additional information which yields a 4 amino acid insert (arg-lys-arg-lys). We present here the nucleotide sequence of the HA gene of this unique isolate and compare it to recent H5N2 and other avian influenza isolates. The complete HA nucleotide sequence of the isolate and phylogenetic relationship suggest that it was derived in direct succession from a non-pathogenic strain isolated about 1 month earlier. The unique insertion sequence is a direct duplication of part of the purine-rich region preceding the arginine codon at the HA cleavage site. This evidence along with other data in this report provide compelling support for a proposed model explaining the mechanism of spontaneous, virulence-related insertions in type A influenza viruses.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chick Embryo
  • Chickens
  • Endopeptidases
  • Hemagglutinins / chemistry*
  • Hemagglutinins / genetics*
  • Hydrolysis
  • Influenza A virus / chemistry
  • Influenza A virus / genetics*
  • Influenza A virus / pathogenicity*
  • Influenza in Birds / virology
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Structure, Secondary
  • Repetitive Sequences, Nucleic Acid*
  • Sequence Alignment
  • Structure-Activity Relationship
  • Virulence


  • Hemagglutinins
  • Endopeptidases

Associated data

  • GENBANK/M10243
  • GENBANK/M18451
  • GENBANK/M30122
  • GENBANK/U20471
  • GENBANK/U37182
  • GENBANK/U79448
  • GENBANK/X07826
  • GENBANK/Z47199