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

J Gen Virol. 2023 Aug;104(8). doi: 10.1099/jgv.0.001881.


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.

Keywords: A/H2N2 virus; HA; airborne transmissibility; receptor specificity; stability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Ferrets
  • Humans
  • Influenza A Virus, H2N2 Subtype* / genetics
  • Influenza A virus*
  • Pandemics