Stability of the influenza virus hemagglutinin protein correlates with evolutionary dynamics

Eili Klein, Deena Blumenkrantz, Adrian Serohijos, Eugene Shakhnovich, Jeong Mo Choi, João V. Rodrigues, Brendan D. Smith, Andrew P Lane, Andrew Feldman, Andrew Pekosz

Research output: Contribution to journalArticle

Abstract

Protein thermodynamics are an integral determinant of viral fitness and one of the major drivers of protein evolution. Mutations in the influenza A virus (IAV) hemagglutinin (HA) protein can eliminate neutralizing antibody binding to mediate escape from preexisting antiviral immunity. Prior research on the IAV nucleoprotein suggests that protein stability may constrain seasonal IAV evolution; however, the role of stability in shaping the evolutionary dynamics of the HA protein has not been explored. We used the full coding sequence of 9,797 H1N1pdm09 HA sequences and 16,716 human seasonal H3N2 HA sequences to computationally estimate relative changes in the thermal stability of the HA protein between 2009 and 2016. Phylogenetic methods were used to characterize how stability differences impacted the evolutionary dynamics of the virus. We found that pandemic H1N1 IAV strains split into two lineages that had different relative HA protein stabilities and that later variants were descended from the higher-stability lineage. Analysis of the mutations associated with the selective sweep of the higher-stability lineage found that they were characterized by the early appearance of highly stabilizing mutations, the earliest of which was not located in a known antigenic site. Experimental evidence further suggested that H1N1 HA stability may be correlated with in vitro virus production and infection. A similar analysis of H3N2 strains found that surviving lineages were also largely descended from viruses predicted to encode more-stable HA proteins. Our results suggest that HA protein stability likely plays a significant role in the persistence of different IAV lineages. 2018 Klein et al.

Original languageEnglish (US)
Article numbere00554-17
JournalmSphere
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Hemagglutinins
Orthomyxoviridae
Protein Stability
Influenza A virus
Proteins
Mutation
Viruses
H1N1 Subtype Influenza A Virus
Pandemics
Virus Diseases
Neutralizing Antibodies
Thermodynamics
Antiviral Agents
Immunity
Hot Temperature

Keywords

  • Evolution
  • Hemagglutinin
  • Influenza
  • Protein stability

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Klein, E., Blumenkrantz, D., Serohijos, A., Shakhnovich, E., Choi, J. M., Rodrigues, J. V., ... Pekosz, A. (2018). Stability of the influenza virus hemagglutinin protein correlates with evolutionary dynamics. mSphere, 3(1), [e00554-17]. https://doi.org/10.1128/mSphere.00554-17

Stability of the influenza virus hemagglutinin protein correlates with evolutionary dynamics. / Klein, Eili; Blumenkrantz, Deena; Serohijos, Adrian; Shakhnovich, Eugene; Choi, Jeong Mo; Rodrigues, João V.; Smith, Brendan D.; Lane, Andrew P; Feldman, Andrew; Pekosz, Andrew.

In: mSphere, Vol. 3, No. 1, e00554-17, 01.01.2018.

Research output: Contribution to journalArticle

Klein, E, Blumenkrantz, D, Serohijos, A, Shakhnovich, E, Choi, JM, Rodrigues, JV, Smith, BD, Lane, AP, Feldman, A & Pekosz, A 2018, 'Stability of the influenza virus hemagglutinin protein correlates with evolutionary dynamics', mSphere, vol. 3, no. 1, e00554-17. https://doi.org/10.1128/mSphere.00554-17
Klein E, Blumenkrantz D, Serohijos A, Shakhnovich E, Choi JM, Rodrigues JV et al. Stability of the influenza virus hemagglutinin protein correlates with evolutionary dynamics. mSphere. 2018 Jan 1;3(1). e00554-17. https://doi.org/10.1128/mSphere.00554-17
Klein, Eili ; Blumenkrantz, Deena ; Serohijos, Adrian ; Shakhnovich, Eugene ; Choi, Jeong Mo ; Rodrigues, João V. ; Smith, Brendan D. ; Lane, Andrew P ; Feldman, Andrew ; Pekosz, Andrew. / Stability of the influenza virus hemagglutinin protein correlates with evolutionary dynamics. In: mSphere. 2018 ; Vol. 3, No. 1.
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