4kpq
Structure and receptor binding specificity of the hemagglutinin H13 from avian influenza A virus H13N6Structure and receptor binding specificity of the hemagglutinin H13 from avian influenza A virus H13N6
Structural highlights
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
|
| ||||||||||||||||||||