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Emerging H5N8 avian influenza viruses

Perspective article argues that #H5N8 avian flu represents a considerable public health concern, particularly considering the 1st human cases of H5N8 infection first reported last December.

The first confirmed outbreak of highly pathogenic avian influenza virus (HPAIV) in birds was documented in Scotland in 1959 with the influenza A H5N1 subtype, although there have been numerous suspected HPAIV outbreaks documented globally since 1878. H5N1 and its genetic reassortants (including H5N2, H5N5, H5N6, and H5N8) have been found to cause thousands of outbreaks worldwide (1, 2) in both farmed poultry and wild birds, with massive mortality. The H5Ny HPAIVs are lethal to most farmed poultry, and culling is often used to prevent further spread. Several of the H5Ny AIVs have zoonotic and pandemic potential because they have been demonstrated to cross the species barrier, transmitting to mammals, including humans. Eurasia and Africa are experiencing a new wave of highly pathogenic H5Ny AIV outbreaks. The zoonotic potential of AIVs warrants continuous, vigilant monitoring to avert further spillovers that could result in disastrous pandemics.

Among the four types (A to D) of influenza viruses, type A tends to be zoonotic, and the natural hosts are regarded to be water birds. Influenza A virus is further divided into different subtypes according to the antigenicity of two viral glycoproteins: hemagglutinin (HA, of which there are 18 subtypes, H1 to H18) and neuraminidase (NA, of which there are 11 subtypes, N1 to N11); most HA-NA combinations in AIVs have been identified. AIVs evolve mainly through two major mechanisms: genetic drift from point mutation(s) and genetic exchange through reassortment of the segmented genomes. Both mechanisms can endow AIVs with new genetic characteristics (sometimes referred to as variants), which may affect transmissibility, pathogenicity, and even antigenicity.

Within a subtype, influenza viruses can be further classified into various clades and subclades generally on the basis of the similarity of the HA gene sequences. Scientists have proposed a unified nomenclature system to describe the constant evolution of the H5Ny AIVs on the basis of the phylogenetic characterization and sequence homology of their HA gene sequences. In this system, new clades and subclades can be designated when their average percentage pairwise nucleotide distances exceed 1.5% from known clades. These are defined as second-, third-, or fourth-order clades and assigned a numerical “address” that links them to their original clade. For example, within the distinct clade 2.1 of H5, third-order clades meeting the clade definition are designated as clades 2.1.1 and 2.1.2, and so on (see the figure).

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