Changes in the hemagglutinin of H5N1 viruses during human infection – Influence on receptor binding☆
نویسندگان
چکیده
As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process.
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 کاملMolecular Identification of Pre-Existing Immunityin Human against H9N2 Influenza Viruses Using HLA-A*0201 Binding Peptides
Background and Aims: The contribution genetic and antigenic diversity of H9N2 influenza viruses in evading from immune responses, cytotoxic T lymphocytes (CTL) epitopes in hemagglutinin (HA) protein restricted by HLA binding peptides was identified. Materials and Methods: Phylogenetic analyses were carried out for all of full length HA and deduced amino acid sequences of H9N2 viruses available ...
متن کاملEffect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses.
Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated ch...
متن کاملPhylogenetic 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 کاملBacillus subtilis as a Host for Recombinant Hemagglutinin Production of the Influenza A (H5N1) Virus
Abstract Background and Aims: Influenza A(H5N1) viruses circulating in animals might evolve and acquire the ability to spread from human to human and thus start a pandemic. Hemagglutinin (HA) has been shown to play a major role in binding of influenza virus to its target cell and the main neutralizing antibody responses elicit against this region. Recent studies have shown that...
متن کامل