Description
HPAIV H5N1 of clade 2.2.1 is endemic in Egypt since 2006 and 2 distinct clades have evolved: clade 2.2.1.1 in commercial poultry and clades 2.2.1.2 and 2.2.1.2a in humans and poultry. Compared to the neuraminidase (NA) of the parental 2.2.1 viruses, avian viruses in clade 2.2.1.1 possessed one mutation (I168T) and human-like viruses in clades 2.2.1.2 and 2.2.1.2a had 4 mutations (A46D, L204M, S319F and S430G) and 16 mutations, respectively. Here, recombinant 2.2.1.2a viruses carrying different NA resembling those in clade 2.2.1, 2.2.1.1 or 2.2.1.2 or single mutations were generated. In vitro, no or minimal impact on replication in cell cultures, plaque size, cleavability, receptor binding activity (RBA) and oseltamivir resistance was observed. Viruses with human-like NA had significantly lower NA activity than viruses with avian-like NA. Reduced NA activity of 2.2.1.2a was due to L204M. Insertion of L204M in H1N1, H5N1 and H7N1 viruses also reduced the NA activity. Over 97% (n=8053) of NA sequences in the GenBank possessed L204. All inoculated chickens died within 3 dpi. In mice, virus with L204M exhibited lower virulence and did not kill all animals, whereas S319F and S430G increased the virulence without remarkable difference in the cellular immune response. Together, H5N1 viruses in humans acquire NA mutations to maximize fitness in mammals without impact on replication in poultry.
| Choose primary session | Pathogenesis |
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| Choose secondary Session | Visualising Flu |
