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Virulence-associated sequence duplication at the hemagglutinin cleavage site of avian influenza viruses
M L Perdue1, M García, D Senne
1Agriculture Research Service, United States Department of Agriculture, Athens, GA, USA.
Abstract:
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.
Insights
Highly pathogenic avian influenza (AI) viruses in Mexico show unique hemagglutinin (HA) gene insertions. These insertions, like arg-lys-arg-lys, may arise spontaneously, increasing AI virus virulence.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Recent highly pathogenic (HP) avian influenza (AI) virus field isolates from Mexico exhibit specific amino acid insertions at the hemagglutinin (HA) glycoprotein cleavage site.
- One HP isolate displays a notable four-amino acid insert (arginine-lysine-arginine-lysine).
Purpose of the Study:
- To present the nucleotide sequence of the HA gene from a unique HP AI virus isolate.
- To compare this sequence with other avian influenza isolates, including H5N2 strains.
- To investigate the phylogenetic relationship and potential origin of the unique insertion.
Main Methods:
- Nucleotide sequencing of the HA gene from the unique HP AI virus isolate.
- Comparative sequence analysis with recent H5N2 and other avian influenza isolates.
- Phylogenetic analysis to determine evolutionary relationships.
Main Results:
- The complete HA nucleotide sequence was determined for the unique isolate.
- Phylogenetic analysis suggests the isolate originated from a non-pathogenic strain isolated approximately one month prior.
- The unique insertion sequence is identified as a direct duplication of a purine-rich region preceding the HA cleavage site's arginine codon.
Conclusions:
- The findings provide strong support for a model explaining spontaneous, virulence-associated insertions in type A influenza viruses.
- The specific insertion mechanism at the HA cleavage site is linked to increased pathogenicity.