Tweet
Virology. 2019 Jul 12;535:232-240. doi: 10.1016/j.virol.2019.07.012. [Epub ahead of print]
Identification of key hemagglutinin residues responsible for cleavage, acid stability, and virulence of fifth-wave highly pathogenic avian influenza A(H7N9) viruses.
Sun X1, Belser JA1, Yang H1, Pulit-Penaloza JA1, Pappas C1, Brock N2, Zeng H1, Creager HM1, Stevens J1, Maines TR3.
Author information
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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
A(H7N9); Acid stability; Fusion; Hemagglutinin cleavage; Influenza virus; Mice; Virulence
PMID: 31325838 DOI: 10.1016/j.virol.2019.07.012
Identification of key hemagglutinin residues responsible for cleavage, acid stability, and virulence of fifth-wave highly pathogenic avian influenza A(H7N9) viruses.
Sun X1, Belser JA1, Yang H1, Pulit-Penaloza JA1, Pappas C1, Brock N2, Zeng H1, Creager HM1, Stevens J1, Maines TR3.
Author information
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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
A(H7N9); Acid stability; Fusion; Hemagglutinin cleavage; Influenza virus; Mice; Virulence
PMID: 31325838 DOI: 10.1016/j.virol.2019.07.012