Identification of amino acids in highly pathogenic avian influenza H5N1 virus hemagglutinin that determine avian influenza species specificity

Abstract

To test the role of neutralizing antibodies (nAbs) and receptor adaptation in interspecies transmission of influenza virus, two H5N1 strains, isolated from human and avian hosts, with four amino acid differences in hemagglutinin (HA) and seven HA mutations were studied. We found that a mutation at amino acid position 90 in the H5N1 HA, outside the receptor-binding domain (RBD), could simultaneously induce changes in the RBD conformation to escape from nAb binding and alter the receptor preference through long-range regulation. This mutation was deemed a "key event" for interspecies transmission. It is likely a result of positive selection caused by antibodies, allowing the original invasion by new species-specific variants. A mutation at amino acid position 160 in the RBD only induced a change in receptor preference. This mutation was deemed a "maintaining adaptation", which ensured that influenza virus variants would be able to infect new organisms of a different species successfully. The mutation is the result of adaptation caused by the receptor. Our results suggest that continuing occurrence of these two types of mutations made the variants persist in the new host species.

Novel Phylogenetic Algorithm to Monitor Human Tropism in Egyptian H5N1-HPAIV Reveals Evolution toward Efficient Human-to-Human Transmission

“…Analysis of all H5N1-HPAIV from Asia, Europe, America and Africa from NCBI and GISAID databases, revealed only 12 H5N1-HPAIV with the mutation 129Δ, and only 9 viruses with the combined mutations 129Δ and I151T. The 129Δ deletion did not occur in H5N1-HPAIV originally introduced into Egypt in 2006 [28], [29]. Isolates from non-human mammals likewise did not reveal the 129Δ.…”

“…In Table 4 are given mutations which increase binding of H5N1-HPAIV HA1 to human receptor [28], [29], [33]–[38], but none of these mutations were found in G1 nor in G2 viruses which supposedly have an increased human tropism. The only exception is the substitution S223N which facilitates α2,6 SA binding.…”

The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells

“…18,19 Briefly, HA ectodomain DNA fragments from three H5N1 strains were cloned into the transfer vector PacGP67b (BD Biosciences, San Diego, CA, USA) and cotransfected with linearized baculovirus DNA into Sf-9 cells for the production of recombinant baculoviruses containing the HA genes. The transfected Sf-9 cells were cultured at 27 uC in Sf-900 II SFM for 4 h before replacement with fresh medium.…”

Antigenic Analyses of Highly Pathogenic Avian Influenza A Viruses

“…(2) Non-RBS globular domain moderately conserved epitopes, comprising ten potential sites (Cao et al 2012;Du et al 2009;Hu et al 2012;Li et al 2011;Oh et al 2010;Prabakaran et al 2009a;Rockman et al 2013). (3) RBS variable epitopes; comprising a total of twenty potential epitopes Ferreira et al 2010;Hanson et al 2006;Ho et al 2009;Hoffmann et al 2005;Kaverin et al 2002Kaverin et al , 2007Khurana et al 2009;Li et al 2009;Masalova et al 2011;Ohkura et al 2012;Prabakaran et al 2009aPrabakaran et al , b, 2010Prabhu et al 2009;Rudneva et al 2010;Sun et al 2009;Wang et al 2009;Yang et al 2007;Yoshida et al 2009).…”