Abstract
An intravenous pathogenicity index (IVPI) of > 1.2 in chickens or, in case of subtypes H5 and H7, expression of a polybasic hemagglutinin cleavage site (HACS), signals high pathogenicity (HP). Viruses of the H9N2-G1 lineage, which spread across Asia and Africa, are classified to be of low pathogenicity although, in the field, they became associated with severe clinical signs and epizootics in chickens. Here we report on a pre-eminent trait of recent H9N2-G1 isolates from Bangladesh and India, which express a tribasic HACS (motif PAKSKR-GLF; reminiscent of an HPAIV-like polybasic HACS) and compare their features to H9Nx viruses with di- and monobasic HACS from other phylogenetic and geographic origins. In an in vitro assay, the tribasic HACS of H9N2 was processed by furin-like proteases similar to bona fide H5 HPAIV while some dibasic sites showed increased cleavability but monobasic HACS none. Yet, all viruses remained trypsin-dependent in cell culture. In ovo, only tribasic H9N2 viruses were found to replicate in a grossly extended spectrum of embryonic organs. In contrast to all subtype H5/H7 HPAI viruses, tribasic H9N2 viruses did not replicate in endothelial cells either in the chorio-allantoic membrane or in other embryonic tissues. By IVPI, all H9Nx isolates proved to be of low pathogenicity. Pathogenicity assessment of tribasic H9N2-G1 viruses remains problematic. It cannot be excluded that the formation of a third basic amino acid in the HACS forms an intermediate step towards a gain in pathogenicity. Continued observation of the evolution of these viruses in the field is recommended.
Highlights
Infections with low pathogenicity avian influenza viruses (LPAIV) of subtype H9N2 remain highly prevalent in poultry in many countries in Asia, the Middle East, and Africa [1]
H9 AIV isolated from recent poultry samples from Asia, Africa, and European countries revealed subtypes H9N2, H9N3, and H9N8, most of them clustering with the G1 lineage, with HA proteins harboring mono, di, or tribasic cleavage site motifs
Tribasic cleavage site motifs are unusual in low pathogenic AIV and, so far, have only been detected in viruses of the H9 subtype
Summary
Infections with low pathogenicity avian influenza viruses (LPAIV) of subtype H9N2 remain highly prevalent in poultry in many countries in Asia, the Middle East, and Africa [1]. Independent of the lineage, all H9 strains are considered to be of low pathogenicity based on the lack of inducing mortality in the standardized in vivo pathotyping tests in chickens [14] Despite their classification as LPAIV, they are associated with severe disease in poultry leading to significant economic losses [15, 16]. There is ample evidence that conversion by spontaneous mutation of a monobasic cleavage site into a polybasic one is at the basis of the pathogenicity shift from LP to HP phenotype in subtypes H5 and H7 [23] Why and when such conversion events occur remains essentially unclear [27]
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