Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 28 September 2019 / Approved: 29 September 2019 / Online: 29 September 2019 (05:21:52 CEST)

A peer-reviewed article of this Preprint also exists.

An, S.-H.; Lee, C.-Y.; Hong, S.-M.; Song, C.-S.; Kim, J.-H.; Kwon, H.-J. 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. Viruses 2019, 11, 923. An, S.-H.; Lee, C.-Y.; Hong, S.-M.; Song, C.-S.; Kim, J.-H.; Kwon, H.-J. 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. Viruses 2019, 11, 923.

Journal reference: Viruses 2019, 11, 923
DOI: 10.3390/v11100923

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, and 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 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.

Subject Areas

clade 2.3.2.1c h5n1 virus; immunity evasion; ha trimer stability; thermostability; mammalian pathogenicity

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