Le Sage, V.; Kormuth, K.A.; Nturibi, E.; Lee, J.M.; Frizzell, S.A.; Myerburg, M.M.; Bloom, J.D.; Lakdawala, S.S. Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model. Viruses2021, 13, 719.
Le Sage, V.; Kormuth, K.A.; Nturibi, E.; Lee, J.M.; Frizzell, S.A.; Myerburg, M.M.; Bloom, J.D.; Lakdawala, S.S. Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model. Viruses 2021, 13, 719.
Airborne transmission of seasonal and pandemic influenza viruses is responsible for their epidemiological success and public health burden in humans. Efficient airborne transmission of H1N1 influenza virus relies on receptor specificity and pH of fusion of the surface glycoprotein hemagglutinin (HA). In this study, we examine the role of HA pH of fusion on transmissibility of a cell culture-adapted H3N2 virus. Mutations in the HA head at positions 78 and 212 of A/Perth/16/2009 (H3N2), which were selected after cell culture adaptation, decrease the acid stability of the virus from a pH of 5.5 (WT) to 5.8 (mutant). In addition, we observed that this mutant H3N2 virus replicated to higher titers in cell culture but had reduced airborne transmission in the ferret model. These data demonstrate that, like H1N1 HA, the pH of fusion for H3N2 HA is a determinant of efficient airborne transmission. Surprisingly, we demonstrate that the NA segment noncoding regions can impact the pH of fusion of reassortant viruses. Taken together, our data confirm that HA acid stability is an important characteristic of epidemiologically successful human influenza viruses and is influenced by HA/NA balance.
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.