A naturally occurring HA-stabilizing amino acid (HA1-Y17) in an A(H9N2) low-pathogenic influenza virus contributes to airborne transmission

• Published in: mBio Vol. 15; no. 1; p. e0295723
• Main Authors: Sun, Xiangjie, Belser, Jessica A, Pulit-Penaloza, Joanna A, Brock, Nicole, Kieran, Troy J, Zeng, Hui, Pappas, Claudia, Tumpey, Terrence M, Maines, Taronna R
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 16-01-2024
• Subjects: acid stability; airborne transmission; Amino Acids; Animals; Ferrets; H9N2; HA fusion activation; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Hemagglutinins; influenza A virus; Influenza A Virus, H9N2 Subtype - genetics; Influenza A Virus, H9N2 Subtype - metabolism; Influenza in Birds; Research Article; Respiratory Aerosols and Droplets; Virology; airborne transmission; HA fusion activation; acid stability; H9N2; influenza A virus
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mbio.02957-23

Despite the accumulation of evidence showing that airborne transmissible influenza A virus (IAV) typically has a lower pH threshold for hemagglutinin (HA) fusion activation, the underlying mechanism for such a link remains unclear. In our study, by using a pair of isogenic recombinant A(H9N2) viruses with a phenotypical difference in virus airborne transmission in a ferret model due to an acid-destabilizing mutation (HA1-Y17H) in the HA, we demonstrate that an acid-stable A(H9N2) virus possesses a multitude of advantages over its less stable counterpart, including better fitness in the ferret respiratory tract, more effective aerosol emission from infected animals, and improved host susceptibility. Our study provides supporting evidence for the requirement of acid stability in efficient airborne transmission of IAV and sheds light on fundamental mechanisms for virus airborne transmission.