Open access
Substitutions affecting the HA–NA–receptor balance preceded the emergence of the pandemic 2009 H1N1 virus
K. Marougka
R. Leiva-Rebollo
Freeke Hofma
A. van Dijk
N. Schuurman
Shervin Kaandorp
Xue-Sheng Wu
Meng-Ying Liu
Louisa Elizabeth Wallace
Le-Meng Chao
Tom Wennekes
Elif Uslu
G. Boons
Loes A. den Hertog-Oosterhoff
G. Amatngalim
E. de Vries
Adolfo García-Sastre
C. D. de Haan
Sep 2026 · Proceedings of the National Academy of Sciences of the United States of America · Vol 123 · 0 citations
· 61 references
Medicine
Abstract
Significance Influenza A pandemics greatly affect the human population every few decades when a novel animal virus breaches the species barrier. The H1N1 pandemic of 2009 (H1N1pdm09) is the first pandemic in the genomics era, which allows us to identify and study in detail mutations in prepandemic swine viruses associated with the jump to humans. Here, we highlight adjustment of the balance between HA-mediated receptor binding and NA-mediated receptor cleavage (HA–NA balance) as a step that occurred in swine prior to the emergence of H1N1pdm09 virus in humans. These findings suggest that not only mutations in HA, but also in NA, may contribute to the pandemic potential of animal viruses.