HA stabilization promotes replication and transmission of swine H1N1 gamma influenza viruses in ferrets

• Published in: eLife Vol. 9
• Main Authors: Hu, Meng, Yang, Guohua, DeBeauchamp, Jennifer, Crumpton, Jeri Carol, Kim, Hyunsuh, Li, Lei, Wan, Xiu-Feng, Kercher, Lisa, Bowman, Andrew S, Webster, Robert G, Webby, Richard J, Russell, Charles J
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 30.06.2020; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Adaptation; Amino acids; Analysis; Animals; California; Canada; Cells (Biology); Disease control; Disease transmission; Epidemics; Ferrets; Genes; HA protein; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Hemagglutinins; Illinois; Infections; Influenza A; influenza A virus; Influenza A Virus, H1N1 Subtype - physiology; Influenza viruses; Lectins; Mammalian cells; Microbiology and Infectious Disease; Mustela; Orthomyxoviridae; Orthomyxoviridae Infections - veterinary; Orthomyxoviridae Infections - virology; Pandemics; pH effects; Proteins; Replication; Risk assessment; Scientific equipment industry; Swine flu; Swine influenza; swine viruses; Tennessee; United States; viral fusion protein; virus adaptation; virus transmissibility; Viruses; Canada; California; United States; Tennessee; Illinois; infectious disease; viral fusion protein; microbiology; virus adaptation; swine viruses; virus; influenza A virus; virus transmissibility
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.56236

Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009-2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5-5.9) than pandemic clade (pH 5.0-5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5-5.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.