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Identification of key hemagglutinin residues responsible for cleavage, acid stability, and virulence of fifth-wave highly pathogenic avian influenza A(H7N9) viruses.

Abstract
We previously demonstrated that despite no airborne transmissibility increase compared to low pathogenic avian influenza viruses, select human isolates of highly pathogenic avian influenza A(H7N9) virus exhibit greater virulence in animal models and a lower threshold pH for fusion. In the current study, we utilized both in vitro and in vivo approaches to identify key residues responsible for hemagglutinin (HA) intracellular cleavage, acid stability, and virulence in mice. We found that the four amino acid insertion (-KRTA-) at the HA cleavage site of A/Taiwan/1/2017 virus is essential for HA intracellular cleavage and contributes to disease in mice. Furthermore, a lysine to glutamic acid mutation at position HA2-64 increased the threshold pH for HA activation, reduced virus stability, and replication in mice. Identification of a key residue responsible for enhanced acid stability of A(H7N9) viruses is of great significance for future surveillance activities and improvements in vaccine stability.
AuthorsXiangjie Sun, Jessica A Belser, Hua Yang, Joanna A Pulit-Penaloza, Claudia Pappas, Nicole Brock, Hui Zeng, Hannah M Creager, James Stevens, Taronna R Maines
JournalVirology (Virology) Vol. 535 Pg. 232-240 (09 2019) ISSN: 1096-0341 [Electronic] United States
PMID31325838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 Elsevier Inc. All rights reserved.
Chemical References
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Virulence Factors
Topics
  • Animals
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Hemagglutinin Glycoproteins, Influenza Virus (chemistry, genetics, metabolism)
  • Humans
  • Hydrogen-Ion Concentration
  • Influenza A Virus, H7N9 Subtype (genetics, growth & development, isolation & purification)
  • Influenza, Human (virology)
  • Mice
  • Orthomyxoviridae Infections (pathology, virology)
  • Protein Stability
  • Proteolysis
  • Virulence
  • Virulence Factors (chemistry, genetics, metabolism)

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