Heider A, Mochalova L, Harder T, Tuzikov A, et al. Alterations in hemagglutinin receptor-binding specificity accompany the emergence of highly pathogenic avian influenza viruses. J Virol 2015 Mar 4. pii: JVI.03304
Highly pathogenic avian influenza viruses (HPAIVs) of hemagglutinin H5 and H7 subtypes emerge after introduction of low pathogenic avian influenza viruses (LPAIVs) from wild birds into poultry flocks followed by subsequent circulation and evolution. The acquisition of multiple basic amino acids at the endoproteolytical cleavage site of the hemagglutinin (HA) is a molecular indicator for high pathogenicity, at least for infections of gallinaceous poultry. Apart from the well-studied significance of the multi-basic HA cleavage site there is only limited knowledge on other alterations in the HA and neuraminidase (NA) molecules associated with changes in tropism during emergence of HPAIVs from LPAIVs. We hypothesized that changes in tropism may require alterations of sialyloligosaccharide specificities of HA and NA. To test this hypothesis we compared a number of LPAIVs and HPAIVs for their HA-mediated binding and NA-mediated desialylation of a set of synthetic receptor analogs, namely, α2-3 sialylated oligosaccharides. NA substrate specificity correlated with structural groups of NAs and did not correlate with pathogenic potential of the virus. In contrast, all HPAIVs differed from LPAIVs by a higher HA receptor-binding affinity towards trisaccharides 3´SLN and SiaLe(c) and by the ability to discriminate between non-fucosylated and fucosylated sialyloligosaccharides 3´SLN and SiaLe(x). These results suggest that alteration of the receptor-binding specificity accompanies emergence of the HPAIV from their low pathogenic precursors.
IMPORTANCE: Here, we have found for the first time correlations of receptor-binding properties of the HA with a highly pathogenic phenotype of poultry viruses. Our study suggests that enhanced receptor-binding affinity of HPAIVs for a typical "poultry-like" receptor, 3´SLN, is provided by substitutions in the receptor binding site of HA which appeared in HA of LPAIVs in a course of transmission of LPAIVs from wild waterfowl into poultry flocks with subsequent adaptation in poultry. The identification of LPAIVs with receptor characteristics of HPAIVs argue that sialic acid-binding specificity of the HA may be used as a novel phenotypic marker of HPAIVs.
See Also:
Latest articles in those days:
- Establishment of Swine Primary Nasal, Tracheal, and Bronchial Epithelial Cell Culture Models for the Study of Influenza Virus Infection 48 minute(s) ago
- Highly pathogenic avian influenza H5N1 virus infections in pinnipeds and seabirds in Uruguay: implications for bird-mammal transmission in South America 53 minute(s) ago
- Development and evaluation of a multiplex real-time RT-PCR assay for simultaneous detection of H5, H7, and H9 subtype avian influenza viruses 14 hours ago
- Evolutionary dynamics and comparative pathogenicity of clade 2.3.4.4b H5 subtype avian influenza viruses, China, 2021~2022 14 hours ago
- Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation 1 days ago
[Go Top] [Close Window]