title: H7N9 influenza outbreak in China 2013: In silico analyses of conserved segments of the hemagglutinin as a basis for the selection of peptide vaccine targets.
abstract: The sudden emergence of a human infecting strain of H7N9 influenza virus in China in 2013 leading to fatalities in about 30% of the cases has caused wide concern that additional mutations in the strain leading to human to human transmission could lead to a deadly pandemic. It may happen in a short time span as the outbreak of H7N9 is more and more recurrent, which implies that H7N9 evolution is speeding up. H7N9 flu strains were not known to infect humans before this attack in China in February 2013 and it was solely an avian strain. While currently available drugs such as oseltamivir have been found to be largely effective against the H7N9, albeit with recent reported cases of development of resistance to the drug, there is a necessity to identify alternatives to combat this disease, especially if it assumes pandemic proportions. In our work, we have tried to investigate for the genetic changes in hemagglutinin (HA) protein sequence that lead to human infection by an avian infecting virus and identify possible peptide targets to design vaccines to control this upcoming risk. We identified three highly conserved regions in all H7 subtypes, of which one particular immunogenic surface exposed region was found to be well conserved in all human infecting H7N9 strains (accessed up to 27th March 2014). Compared to H7N9 avian strains, we identified two mutations in this conserved region at the receptor binding site of all post-February 2013 human-infecting H7N9China hemagglutinin protein sequences. One of the mutations is very close (3.6 Å) to the hemagglutinin sialic acid binding pocket that may lead to better binding to human host's sialic acid due to the changes in hydrophobicity of the microenvironment of the binding site. We found that the peptide region with these mutational changes that are specific for human infecting H7N9 virus possess the possibility of being used as target for a peptide vaccine.
authors.affiliation: Physics Department, Jadavpur University, Kolkata 700032, India. Electronic address: tapati.sarkar@yahoo.com.
authors.forename: Tapati
authors.initials: T
authors.lastname: Sarkar
authors.affiliation: Physics Department, Jadavpur University, Kolkata 700032, India.
authors.forename: Sukhen
authors.initials: S
authors.lastname: Das
authors.affiliation: Centre for Interdisciplinary Research and Education, 404B Jodhpur Park, Kolkata 700068, India.
authors.forename: Antara
authors.initials: A
authors.lastname: De
authors.affiliation: Centre for Interdisciplinary Research and Education, 404B Jodhpur Park, Kolkata 700068, India.
authors.forename: Papiya
authors.initials: P
authors.lastname: Nandy
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Chawla-Sarkar
authors.affiliation: Centre for Interdisciplinary Research and Education, 404B Jodhpur Park, Kolkata 700068, India.
authors.forename: Ashesh
authors.initials: A
authors.lastname: Nandy
mesh_terms: D002681:China; D003198:Computer Simulation; D006388:Hemagglutinins / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000737:chemistry* / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D006388:Hemagglutinins; D007252:Influenza Vaccines
keywords: Bioinformatics; Graphical representation and numerical characterization; H7N9 conserved regions; Influenza virus; Peptide vaccine