Pleiotropic effects of hemagglutinin amino acid substitutions of influenza A(H1N1)pdm09 virus escape mutants

Virus Research
Irina RudnevaNikolai Kaverin

Abstract

In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We investigated pH optimum of fusion, temperatures of HA heat inactivation, in vivo and in vitro replication kinetics, and connectivity with panel of sera of survivors patients in different epidemic seasons of the previously obtained influenza H1 escape mutants. Our results showed that N133D (H3 numbering) mutation significantly lowered the pH of fusion optimum. Several amino acid substitutions, including K163 N, Q192 L, D190E, G228E, and K285 M, reduced the stability of HA as determined by heat inactivation, whereas A198E substitution is associated with significant increase in HA thermostability compared to the wild-type virus. We found that amino acid change D190 N was associated with a significant decrease in viral growth in eggs and mice. Our potential antigenic variants, except readapted variant, which contained A198E mutation, did not reach fixation in infected people. Overall, a co-variation between antigenic specificity and different HA phenotypic properties was demonstrated.

References

Mar 1, 1992·Microbiological Reviews·R G WebsterY Kawaoka
Nov 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·G W BothE D Kilbourne
Sep 28, 2005·The Journal of General Virology·Irina A RudnevaNikolai V Kaverin
Nov 11, 2009·Science·Scott E HensleyJonathan W Yewdell
Oct 29, 2013·Biochimica Et Biophysica Acta·Caroline M MairChristian Sieben
May 13, 2015·Influenza and Other Respiratory Viruses·Hang K L NguyenMai Q Lê
Jul 30, 2015·Virus Research·Nikolai V KaverinNatalia A Ilyushina
Aug 31, 2016·Nature Microbiology·Chengjun LiYoshihiro Kawaoka
Sep 3, 2016·Archives of Virology·Irina A RudnevaNatalia A Ilyushina

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Citations

Nov 27, 2019·Veterinary Microbiology·Heather VinsonSheela Ramamoorthy

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