The hemagglutininesterase fusion glycoprotein is a primary determinant of the exceptional thermal and acid stability of influenza D virus

Jieshi Yu, Busha Hika, Runxia Liu, Zizhang Sheng, Ben M. Hause, Feng Li, Dan Wang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Influenza D virus (IDV) is unique among four types of influenza viruses in that it utilizes cattle as a primary reservoir. The thermal and acid stability of IDV were examined and directly compared with those of influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The results of our experiments demonstrated that only IDV had a high residual infectivity (~2.5 log units of 50% tissue culture infective dose [TCID50]/ml) after a 60-min exposure to 53°C in solution at a neutral pH, and remarkably, IDV retained this infectivity even after exposure to 53°C for 120 min. Furthermore, the data showed that IDV was extremely resistant to inactivation by low pH. After being treated at pH 3.0 for 30 min, IDV lost only approximately 20% of its original infectiousness, while all other types of influenza viruses were completely inactivated. Finally, replacement of the hemagglutinin (HA) and neuraminidase (NA) proteins of a temperature- and acid-sensitive IAV with the hemagglutinin-esterase fusion (HEF) protein of a stable IDV through a reverse genetic system largely rendered the recombinant IAVs resistant to high-temperature and low-pH treatments. Together, these results indicated that the HEF glycoprotein is a primary determinant of the exceptional temperature and acid tolerance of IDV. Further investigation into the viral entry and fusion mechanism mediated by the intrinsically stable HEF protein of IDV may offer novel insights into how the fusion machinery of influenza viruses evolve to achieve acid and thermal stability, which as a result promotes the potential to transmit across mammal species.

Original languageEnglish
Article numbere00254-17
JournalmSphere
Volume2
Issue number4
DOIs
StatePublished - Jul 1 2017

Bibliographical note

Funding Information:
We thank all of the members of the Li and Wang laboratories for their input into this work; we especially appreciate Hunter Nedland's help proofreading the manuscript. We thank Peter Palese (Mt. Sinai Medical School, New York) for providing the C/Johannesburg/ 1/66 virus. Special thanks to Thomas Rowe, Ruben Donis, and Xiyan Xu from the CDC for their generous support in providing influenza B virus strains. We thank NIAID Biodefense and Emerging Infections Research Resources Repository (BEI Resources) for providing some reagents used in this study. This work was partially supported by NIH grant AI107379, by SDSU AES 3AH-477, by National Science Foundation/EPSCoR (http://www.nsf.gov/od/iia/programs/epscor/ index.jsp) award IIA-1335423, and by the state of South Dakota's Governor's Office of Economic Development as a South Dakota Research Innovation Center

Publisher Copyright:
© 2017 Yu et al.

Keywords

  • Acid stability
  • Hemagglutinin-esterase fusion protein
  • Influenza virus
  • Thermal stability

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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