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Structure and receptor binding specificity of the hemagglutinin H13 from avian influenza A virus H13N6
Structural highlights
FunctionHEMA_I77AF Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore. Publication Abstract from PubMedInterspecies transmission or host switch/jump of influenza viruses is a key scientific question that must be addressed. In addition to the vigorous research on highly pathogenic avian influenza viruses (HPAIVs), studies of the mechanism of interspecies transmission of low pathogenic avian influenza viruses (LPAIVs) could also provide insights into host tropism and virulence evolution. Influenza A virus harboring hemagglutinin (HA) H13 (e.g., H13N6) is an LPAIV. In this study, soluble H13HA glycoprotein was purified, and its receptor binding activity was characterized. The results revealed that H13 exclusively binds the avian alpha2-3-linked sialic acid receptor; no binding was detected to the mammalian alpha2-6-linked sialic acid receptor. Furthermore, the molecular basis of the H13 receptor binding specificity was revealed by comparative analysis of the crystal structures of both receptor-bound H13 and H5 HAs, which might be contributed by the hydrophobic residue V186. A H13N186 mutant work confirmed the importance of V186 in the receptor binding specificity of H13 HA, which shows that the mutant protein reduced the binding of avian receptor analog but increased the binding of human receptor analog. Detailed structural analysis also demonstrated that the conserved binding sites of the recently well-studied broadly neutralizing human monoclonal antibodies targeting the HA2 domain are found in H13. Our results expand our understanding of virulence evolution, receptor binding preference, and species tropism of the LPAIVs and HPAIVs. Structure and receptor binding specificity of the hemagglutinin H13 from avian influenza A virus H13N6.,Lu X, Qi J, Shi Y, Wang M, Smith DF, Heimburg-Molinaro J, Zhang Y, Paulson JC, Xiao H, Gao GF J Virol. 2013 Jun 12. PMID:23760233[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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