Novel mutations evading avian immunity around the receptor binding site of the clade 2.3.2.1c hemagglutinin gene reduce viral thermostability and mammalian pathogenicity

Se Hee An, Chung Young Lee, Seung Min Hong, Chang Seon Song, Jae Hong Kim, Hyuk Joon Kwon

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Since 2007, highly pathogenic clade 2.3.2 H5N1 avian influenza A (A(H5N1)) viruses have evolved to clade 2.3.2.1a, b, and c; currently only 2.3.2.1c A(H5N1) viruses circulate in wild birds and poultry. During antigenic evolution, clade 2.3.2.1a and c A(H5N1) viruses acquired both S144N and V223I mutations around the receptor binding site of hemagglutinin (HA), with S144N generating an N-glycosylation sequon. We introduced single or combined reverse mutations, N144S and/or I223V, into the HA gene of the clade 2.3.2.1c A(H5N1) virus and generated PR8-derived, 2 + 6 recombinant A(H5N1) viruses. When we compared replication efficiency in embryonated chicken eggs, mammalian cells, and mice, the recombinant virus containing both N144S and I223V mutations showed increased replication efficiency in avian and mammalian hosts and pathogenicity in mice. The N144S mutation significantly decreased avian receptor affinity and egg white inhibition, but not all mutations increased mammalian receptor affinity. Interestingly, the combined reverse mutations dramatically increased the thermostability of HA. Therefore, the adaptive mutations possibly acquired to evade avian immunity may decrease viral thermostability as well as mammalian pathogenicity.

Original languageEnglish
Article number923
JournalViruses
Volume11
Issue number10
DOIs
StatePublished - 9 Oct 2019

Keywords

  • Clade 2.3.2.1c H5N1 virus
  • HA trimer stability
  • Immunity evasion
  • Mammalian pathogenicity
  • Thermostability

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