Deduced amino acid sequences at the haemagglutinin cleavage site of avian influenza A viruses of H 5 and H 7 subtypes

Abstract

The amino acid sequences at the haemagglutinin cleavage sites of 9 avian influenza A viruses of H5 subtype (5 high and 4 low pathogenicity for chickens) and 21 of H7 subtype (13 high and 8 low pathogenicity for chickens) were determined by direct RNA sequencing, PCR amplification sequencing or both. None of the viruses of low pathogenicity had multiple basic amino acids at the cleavage site. All highly pathogenic viruses had an insert of basic amino acids at the cleavage site, except A/chicken/Scotland/59 (H5N1) for which the multiple basic amino acids appeared as substitutions and not insertions. All highly pathogenic viruses examined conformed to the amino acid motif of R-X-R/K-R at the cleavage site which is considered to be essential for high pathogenicity in chickens, with the notable exception of highly pathogenic virus A/turkey/England/50-92/91 (H5N1) which had the sequence R-K-R-K-T-R adjacent to the cleavage site.

Heterogeneity in the haemagglutinin gene and emergence of the highly pathogenic phenotype among recent H5N2 avian influenza viruses from Mexico

“…It may thus represent the first documentation of the proposed insertional event in natural isolates. Although a progenitor to this English HP virus was not directly demonstrated, preceding nHP isolates with very similar cleavage site sequences as the nHP Mexican HSN2 isolates in this study were present (Wood et al, 1993; Table 3). …”

“…In naturally occurring HP avian influenza viruses, increased pathogenicity is primarily correlated with an increase in the number of basic amino acids near the proteolytic cleavage site preceding the fusion peptide (Bosch et aI., 1981;Kawaoka et al, 1987;De et al, 1988;Klenk & Rott, 1988;Philpott et al, 1990;Wood et al, 1993Wood et al, , 1994.…”

Highly pathogenic avian influenza viruses with low virulence for chickens inin vivotests

“…the respiratory and intestinal tracts). In contrast, HPAI viruses possess multiple basic amino acids at their HA0 cleavage sites either as a result of apparent insertion or apparent substitution Wood et al, 1993;Senne et al, 1996), and appear to be cleavable by a ubiquitous protease(s), probably one or more proprotein-processing subtilisin-related endoproteases of which furin is the leading candidate (Stieneke-Grober et al, 1992). These viruses are able to replicate throughout the bird, damaging vital organs and tissues, which results in disease and death (Rott, 1992).…”

Amino acids adjacent to the haemagglutinin cleavage site are relevant for virulence of avian influenza viruses of subtype H5

“…Remarkably, there are some H5 HPAIVs that have polybasic HA cleavage motifs with threonine at P2 Garten & Klenk, 2008;Horimoto et al, 1995a;Pasick et al, 2005;Perdue et al, 1996Perdue et al, , 1997Saito et al, 1994;Suarez et al, 2004;Wood et al, 1993). These examples indicate that threonine at P2 does not impair the virulence of HPAIVs.…”