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United States Department of Agriculture

Agricultural Research Service

Title: Virulence-Associated Sequence Duplication at the Hemagglutinin Cleavage Site of Avian Influenza Viruses

Authors
item Perdue, Michael
item Garcia, Maricarmen
item Senne, Dennis - APHIS, NAT.VET.SERV.LAB
item Fraire, M. - MEXICO

Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 18, 1997
Publication Date: N/A

Interpretive Summary: Avian influenza (AI) isolates which are highly lethal in chickens are appearing worldwide with an increasing frequency. Most of these isolates now have genetic insertions in the hemagglutinin gene which results in a hemagglutinin protein with an increased number of basic amino acids at the proteolytic cleavage site (PCS). It is the structure of this PCS which is s most important in specifying whether the virus will be lethal in commercial poultry. In this study we have characterized the PCS of a new highly chicken-lethal isolate from the ongoing outbreak of AI in central Mexico. The data we have obtained by comparing this isolate with other isolates from Mexico as well as isolates from around the globe have led us to propose a model whereby genetic insertions may occur in avian influenza viruses and give rise to lethal mutants. The data and new method of analyzing it presented in this manuscript, may someday allow prediction of f the likelihood that a circulating non-pathogenic isolate will become highly lethal.

Technical 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 (Swayne and Perdue, 1995; Garcia et al. 1996). One HP isolate has additional information which yields a four amino acid insert (arg-lys-arg- - lys). We present here the nucleotide sequence of the HA gene of this unique isolate and compare it with recent H5N2 and other avian influenza isolates. The complete HA nucleotide sequence of the isolate and phylogenetic relationship demonstrate that it was derived in direct succession from a non-pathogenic strain isolated about one month earlier. The unique insertion sequence is a direct duplication of part of the purine-rich region preceding the arginine codon of 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 strains.

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