Continued adaptation of A/H2N2 viruses during pandemic circulation in humans

Jasmin S. Kutter, Martin Linster, Dennis de Meulder, Theo M. Bestebroer, Pascal Lexmond, Miruna E. Rosu, Mathilde Richard, Robert P. de Vries, Ron A.M. Fouchier, Sander Herfst*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Influenza A viruses of the H2N2 subtype sparked a pandemic in 1957 and circulated in humans until 1968. Because A/H2N2 viruses still circulate in wild birds worldwide and human population immunity is low, the transmissibility of six avian A/H2N2 viruses was investigated in the ferret model. None of the avian A/H2N2 viruses was transmitted between ferrets, suggesting that their pandemic risk may be low. The transmissibility, receptor binding preference and haemagglutinin (HA) stability of human A/H2N2 viruses were also investigated. Human A/H2N2 viruses from 1957 and 1958 bound to human-type α2,6-linked sialic acid receptors, but the 1958 virus had a more stable HA, indicating adaptation to replication and spread in the new host. This increased stability was caused by a previously unknown stability substitution G205S in the 1958 H2N2 HA, which became fixed in A/H2N2 viruses after 1958. Although individual substitutions were identified that affected the HA receptor binding and stability properties, they were not found to have a substantial effect on transmissibility of A/H2N2 viruses via the air in the ferret model. Our data demonstrate that A/H2N2 viruses continued to adapt during the first year of pandemic circulation in humans, similar to what was previously shown for the A/H1N1pdm09 virus.

Original languageEnglish
Article number001881
JournalThe Journal of general virology
Issue number8
Publication statusPublished - 31 Aug 2023

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