Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA Strain

The need for a vaccine/inhibitor design has become inevitable concerning the emerging epidemic and pandemic viral infections, and the recent outbreak of the influenza A (H1N1) virus is one such example. From 2009 to 2018, India faced severe fatalities due to the outbreak of the influenza A (H1N1) vi...

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Main Authors: Shilpa Sri Pushan, Mahesh Samantaray, Muthukumaran Rajagopalan, Amutha Ramaswamy
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1111869/full
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author Shilpa Sri Pushan
Mahesh Samantaray
Muthukumaran Rajagopalan
Amutha Ramaswamy
author_facet Shilpa Sri Pushan
Mahesh Samantaray
Muthukumaran Rajagopalan
Amutha Ramaswamy
author_sort Shilpa Sri Pushan
collection DOAJ
description The need for a vaccine/inhibitor design has become inevitable concerning the emerging epidemic and pandemic viral infections, and the recent outbreak of the influenza A (H1N1) virus is one such example. From 2009 to 2018, India faced severe fatalities due to the outbreak of the influenza A (H1N1) virus. In this study, the potential features of reported Indian H1N1 strains are analyzed in comparison with their evolutionarily closest pandemic strain, A/California/04/2009. The focus is laid on one of its surface proteins, hemagglutinin (HA), which imparts a significant role in attacking the host cell surface and its entry. The extensive analysis performed, in comparison with the A/California/04/2009 strain, revealed significant point mutations in all Indian strains reported from 2009 to 2018. Due to these mutations, all Indian strains disclosed altered features at the sequence and structural levels, which are further presumed to be associated with their functional diversity as well. The mutations observed with the 2018 HA sequence such as S91R, S181T, S200P, I312V, K319T, I419M, and E523D might improve the fitness of the virus in a new host and environment. The higher fitness and decreased sequence similarity of mutated strains may compromise therapeutic efficacy. In particular, the mutations observed commonly, such as serine-to-threonine, alanine-to-threonine, and lysine-to-glutamine at various regions, alter the physico-chemical features of receptor-binding domains, N-glycosylation, and epitope-binding sites when compared with the reference strain. Such mutations render diversity among all Indian strains, and the structural and functional characterization of these strains becomes inevitable. In this study, we observed that mutational drift results in the alteration of the receptor-binding domain, the generation of new variant N-glycosylation along with novel epitope-binding sites, and modifications at the structural level. Eventually, the pressing need to develop potentially distinct next-generation therapeutic inhibitors against the HA strains of the Indian influenza A (H1N1) virus is also highlighted here.
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spelling doaj.art-8b5ce842cdd742c7ac95190ecb9db3562023-03-16T07:22:15ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-03-011010.3389/fmolb.2023.11118691111869Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA StrainShilpa Sri Pushan0Mahesh Samantaray1Muthukumaran Rajagopalan2Amutha Ramaswamy3Department of Bioinformatics, Pondicherry University, Puducherry, IndiaDepartment of Bioinformatics, Pondicherry University, Puducherry, IndiaDepartment of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, IndiaDepartment of Bioinformatics, Pondicherry University, Puducherry, IndiaThe need for a vaccine/inhibitor design has become inevitable concerning the emerging epidemic and pandemic viral infections, and the recent outbreak of the influenza A (H1N1) virus is one such example. From 2009 to 2018, India faced severe fatalities due to the outbreak of the influenza A (H1N1) virus. In this study, the potential features of reported Indian H1N1 strains are analyzed in comparison with their evolutionarily closest pandemic strain, A/California/04/2009. The focus is laid on one of its surface proteins, hemagglutinin (HA), which imparts a significant role in attacking the host cell surface and its entry. The extensive analysis performed, in comparison with the A/California/04/2009 strain, revealed significant point mutations in all Indian strains reported from 2009 to 2018. Due to these mutations, all Indian strains disclosed altered features at the sequence and structural levels, which are further presumed to be associated with their functional diversity as well. The mutations observed with the 2018 HA sequence such as S91R, S181T, S200P, I312V, K319T, I419M, and E523D might improve the fitness of the virus in a new host and environment. The higher fitness and decreased sequence similarity of mutated strains may compromise therapeutic efficacy. In particular, the mutations observed commonly, such as serine-to-threonine, alanine-to-threonine, and lysine-to-glutamine at various regions, alter the physico-chemical features of receptor-binding domains, N-glycosylation, and epitope-binding sites when compared with the reference strain. Such mutations render diversity among all Indian strains, and the structural and functional characterization of these strains becomes inevitable. In this study, we observed that mutational drift results in the alteration of the receptor-binding domain, the generation of new variant N-glycosylation along with novel epitope-binding sites, and modifications at the structural level. Eventually, the pressing need to develop potentially distinct next-generation therapeutic inhibitors against the HA strains of the Indian influenza A (H1N1) virus is also highlighted here.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1111869/fullinfluenza AH1N1virusphylogenetic analysisantigenic siteN-glycosylation
spellingShingle Shilpa Sri Pushan
Mahesh Samantaray
Muthukumaran Rajagopalan
Amutha Ramaswamy
Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA Strain
Frontiers in Molecular Biosciences
influenza A
H1N1
virus
phylogenetic analysis
antigenic site
N-glycosylation
title Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA Strain
title_full Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA Strain
title_fullStr Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA Strain
title_full_unstemmed Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA Strain
title_short Evolution of Indian Influenza A (H1N1) Hemagglutinin Strains: A Comparative Analysis of the Pandemic Californian HA Strain
title_sort evolution of indian influenza a h1n1 hemagglutinin strains a comparative analysis of the pandemic californian ha strain
topic influenza A
H1N1
virus
phylogenetic analysis
antigenic site
N-glycosylation
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1111869/full
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