Intersegmental recombination between the haemagglutinin and matrix genes was responsible for the emergence of a highly pathogenic H7N3 avian influenza virus in British Columbia

Abstract

In February 2004 a highly pathogenic avian influenza (HPAI) outbreak erupted in British Columbia. Investigations indicated that the responsible HPAI H7N3 virus emerged suddenly from a low pathogenic precursor. Analysis of the haemagglutinin (HA) genes of the low and high pathogenic viruses isolated from the index farm revealed the only difference to be a 21 nt insert at the HA cleavage site of the highly pathogenic avian influenza virus. It was deduced that this insert most probably arose as a result of non-homologous recombination between the HA and matrix genes of the same virus. Over the course of the outbreak, a total of 37 isolates with, and 3 isolates without inserts were characterized. The events described here appear very similar to those which occurred in Chile in 2002 where the virulence shift of another H7N3 virus was attributed to non-homologous recombination between the HA and nucleoprotein genes.

First field evidence of the evolution from a non-virulent HPR0 to a virulent HPR-deleted infectious salmon anaemia virus

“…This is consistent with the hypothesis that these two mutations, the HPR deletion in the HE gene and the Q 266 L substitution in the F gene, represent necessary mutational steps for the transition to virulence in ISAV [18,22]. This is also in agreement with observations in avian influenza (AI) where highly pathogenic AI viruses (HPAIV) arise from low-pathogenic AI viruses (LPAIV) by mutations of specific virulence markers and where the acquisition and increase in virulence is a stepwise process [36][37][38][39][40][41]. Although the role of other proteins than HE and F in ISAV pathogenesis so far remains elusive, further mutations of other proteins are expected to increase virulence [11,22,42,43] as demonstrated in other members of the orthomyxovirus family, e.g.…”

Protective measures and human antibody response during an avian influenza H7N3 outbreak in poultry in British Columbia, Canada

“…Within days, the virus causing this outbreak had converted from low to high pathogenicity on the index farm. 18 Ultimately, 42 commercial farms and 11 backyard flocks, comprising 1.3 million birds, were considered infected (Fig. 1).…”

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

“…Vey et al, (1992) suggested that the probable minimum requirement is RXR/KR*GLF, but several very virulent virus do not entirely comply with this minimum. A/turkey/England/50-92/91 (H5N1), with a motif of PQRKRKTR*GLF (Horimoto et al, 1995), and A/chicken/Pennsylvania/1370/83 (H5N2), motif PQKKKR*GLF, do not comply *and nor do the Chile 2002 (Suarez et al, 2004) and the Canada 2004 (Pasick et al, 2005) H7N3 HPAI viruses as discussed below.…”

“…A/chicken/Scotland/59 (H5N1), which has the motif PQRKKR*GLF), while others have insertions without repeating nucleotides. The Chile 2002 (Suarez et al, 2004) and the Canada 2004 (Pasick et al, 2005) H7N3 HPAI viruses show distinct and unusual cleavage site amino acid sequences of PEKPKTCSPLSR CRETR*GLF and PENPKQAYRKRMTR*GLF, respectively. These viruses appear to have arisen as a result of a recombination event between the HA gene and the nucleoprotein gene and matrix gene, respectively, resulting in an insertion at the HA0 cleavage site of 11 amino acids for the Chile virus and of seven amino acids for the Canadian virus.…”