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Open AccessArticle

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

1
Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
2
Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
3
Laboratory of Avian Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
4
Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
5
Laboratory of Poultry Medicine, Department of Farm Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
6
Farm Animal Clinical Training and Research Center (FACTRC), GBST, Seoul National University, Kangwon-do 88026, Korea
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(10), 923; https://doi.org/10.3390/v11100923
Received: 24 September 2019 / Revised: 6 October 2019 / Accepted: 8 October 2019 / Published: 9 October 2019
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: clade 2.3.2.1c H5N1 virus; immunity evasion; HA trimer stability; thermostability; mammalian pathogenicity clade 2.3.2.1c H5N1 virus; immunity evasion; HA trimer stability; thermostability; mammalian pathogenicity
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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.

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