Networks link antigenic and receptor-binding sites of influenza hemagglutinin: mechanistic insight into fitter strain propagation.

Scientific Reports
Venkataramanan SoundararajanRam Sasisekharan

Abstract

Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza strains. To understand this phenomenon, we computed the Significant Interactions Network (SIN) for each residue and mapped the networks of antigenic site residues on a representative H1N1 HA. Specific antigenic site residues are 'linked' to receptor-binding site (RBS) residues via their SIN and mutations within "RBS-linked" antigenic residues can significantly influence receptor-binding affinity by impacting the SIN of key RBS residues. In contrast, other antigenic site residues do not have such "RBS-links" and do not impact receptor-binding affinity upon mutation. Thus, a potential mechanism emerges for how immunologic pressure on RBS-linked antigenic residues can contribute to evolution of fitter influenza strains by modulating the host receptor-binding affinity.

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Feb 27, 2010·PloS One·Venkataramanan SoundararajanRam Sasisekharan

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Citations

Feb 6, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Paul S WikramaratnaSunetra Gupta
Apr 22, 2015·Meta Gene·Yoshiyuki Suzuki
Jan 28, 2014·Genes & Genetic Systems·Yoshiyuki Suzuki
Aug 19, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kannan TharakaramanZachary Shriver
Apr 29, 2015·Current Opinion in Virology·Karthik ViswanathanGregory J Babcock
Jun 12, 2013·Cell·Kannan TharakaramanRam Sasisekharan
Mar 5, 2016·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·A AntónT Pumarola
Nov 12, 2016·ELife·Marc LipsitchColin A Russell
May 31, 2012·The Biochemical Journal·Akila JayaramanRam Sasisekharan
Oct 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Anfisa V PopovaGeorgii A Bazykin
Feb 15, 2014·Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin·Dm SkowronskiY Li
Jan 1, 2013·Mikrochimica Acta·Tomáš BertókJan Tkac
Dec 18, 2020·Expert Opinion on Pharmacotherapy·Qiao ZhangShuwen Liu
Apr 8, 2021·The New England Journal of Medicine·Ram Sasisekharan

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Software Mentioned

python
SIN
MATLAB
Phylowidget
R script
Pymol
Accelrys Discovery Studio
Jalview

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