Structure and receptor binding specificity of hemagglutinin H13 from avian influenza A virus H13N6.

نویسندگان

  • Xishan Lu
  • Jianxun Qi
  • Yi Shi
  • Ming Wang
  • David F Smith
  • Jamie Heimburg-Molinaro
  • Yanfang Zhang
  • James C Paulson
  • Haixia Xiao
  • George F Gao
چکیده

Interspecies transmission (host switching/jumping) 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 viruses harboring hemagglutinin (HA) H13 (e.g., H13N6) are LPAIVs. In this study, soluble H13 HA glycoprotein was purified, and its receptor binding activity was characterized. The results revealed that H13 exclusively binds the avian α2-3-linked sialic acid receptor; no binding to the mammalian α2-6-linked sialic acid receptor was detected. 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. Work with an H13N186 mutant confirmed the importance of V186 in the receptor binding specificity of H13 HA, which shows that the mutant protein reduced the binding of an avian receptor analog but increased the binding of a 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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Amino Acid Sequence Analysis of Hemagglutinin Protein of H9N2 Isolated from Broilers in Tehran in 2007

Background and Aims: Since 1998, Iranian poultry industry has been affected by avian influenza (AI) virus, subtype H9N2. The association of high mortality and case report of H5N1 and H9N2 influenza virus in wild birds in recent years raised the suspicion of a possible new genetic modified AI virus. Methods: Partial nucleotide sequences and deduced amino acid of hemagglutinin (HA) genes of 4 H9...

متن کامل

Phylogenetic Analysis of Hemagglutinin Gene of H9N2 Avian Influenza Viruses Isolated from Chicken in Iran in 2010-2011: Emerging of a New Subgroup

Background and Aims: Hemagglutinin (HA) protein of Avian Influenza (AI) plays an essential role in the virus pathogenicity. AI H9N2 subtype causes significant economic loss in broiler and layer in poultry farms in Iran. AI viruses have a great involvement in evolutionary changes at nucleotide and amino acid levels and vaccines could induce faster rates of such changes. Up-dated understanding of...

متن کامل

Role of sialic acid binding specificity of the 1918 influenza virus hemagglutinin protein in virulence and pathogenesis for mice.

The 1918 influenza pandemic caused more than 40 million deaths and likely resulted from the introduction and adaptation of a novel avian-like virus. Influenza A virus hemagglutinins are important in host switching and virulence. Avian-adapted influenza virus hemagglutinins bind sialic acid receptors linked via alpha2-3 glycosidic bonds, while human-adapted hemagglutinins bind alpha2-6 receptors...

متن کامل

Sequence Analysis and Phylogenetic Study of Hemagglutinin Gene of H9N2 Subtype of Avian Influenza Virus Isolated during 1998-2002 in Iran

Sequence analysis and phylogenetic study of hemagglutinin (HA) gene of H9N2 subtype of avian influenza virus isolates (outbreaks of 1998-2002) in Tehran province (Iran) were studied. Two sets of forward and reverse primers in highly conserved regions, based on sequences of HA gene in Genbank, were designed. PCR products of a 430-bp fragment of 16 isolates were sequenced and then were aligned wi...

متن کامل

Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity.

Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for alpha2,6- rather than alpha2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing alpha2,3- or increasing al...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of virology

دوره 87 16  شماره 

صفحات  -

تاریخ انتشار 2013