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Appearance of L90I and N205S Mutations in Effector Domain of NS1 Gene of pdm (09) H1N1 Virus from India during 2009–2013

DOI: 10.1155/2014/861709

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Abstract:

In the present study, full length sequencing of NS gene was done in 91 samples which were obtained from patients over the time period of five years from 2009 to 2013. The sequencing of NS gene was undertaken in order to determine the changes/mutations taking place in the NS gene of A H1N1 pdm (09) since its emergence in 2009. Analysis has shown that the majority of samples belong to New York (G1 type) strain with valine at position 123. Effector domain of NS1 protein displays the appearance of three mutations L90I, I123V, and N205S in almost all the samples from 2010 onwards. Phylogenetic analysis of available NS1 sequences from India has grouped all the sequences into four clusters with mean genetic distance ranging from 12% to 24% between the clusters. Variability in length of NS1 protein was seen in sequences from these clusters, 230-amino-acid-residue NS1 for all strains from year 2007 to 2008 and for 21 strains from year 2009 and 219-residue products for 37 strains from year 2009 and all strains from year 2010 to 2013. Mutations like K62R, K131Q, L147R, and A202P were observed for the first time in NS1 protein and their function remains to be determined. 1. Introduction Influenza viruses are responsible for acute respiratory infection and are a source of seasonal epidemics and occasional pandemics. Influenza A viruses are classified into subtypes based on the different types of HA and NA combinations that occur. So far 18 hemagglutinin (HA) and 11 neuraminidase (NA) subtypes have been reported from various organisms ranging between aquatic, avian, and human species [1, 2]. Segment 8 of influenza A (H1N1) encodes two proteins NS1 (nonstructural) protein and NEP (nuclear export protein) by alternative splicing. The mRNAs of both proteins share 56 nucleotides at the 5′ end, resulting in both proteins sharing 10 amino acids at N terminal. NS1 protein is encoded by the collinear mRNA from segment 8 of the influenza virus genome and has a strain specific length ranging from 230 to 237 amino acid residues. It is expressed exclusively in the infected cells [3]. NS1 could be divided into two functional domains: (i) N-terminal RNA binding domain (residues 1–73) and (ii) C-terminal effector domain, interacting with several host factors (residues 74–230) [3–6]. NS1 is a multifunctional protein involved in various functions of regulating immune responses. It functions as an interferon (IFN) antagonist, which allows efficient virus replication in IFN-competent hosts. NS1 targets both IFN- production and the activation of IFN-induced antiviral genes [6]. The RNA

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