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장승규Seung-Gyu Jang

충북대학교

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Emerg. Microbes Infect., Jan 08 2024, | https://doi.org/10.1080/22221751.2024.2302854 HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts

Seung-Gyu Jang ^1†, Young-Il Kim ^2†, Mark Anthony B Casel ^1,2, Jeong Ho Choi ¹, Ju Ryeon Gil ¹, Rare Rollon ¹, Eun-Ha Kim ², Se-Mi Kim ², Ho Young Ji ², Dong Bin Park ², Jungwon Hwang ³, Jae-Woo Ahn ², Myung Hee Kim ³, Min-Suk Song ^1,4, Young Ki Choi^1,2,4

¹College of Medicine and Medical Research Institute, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, 28644, Republic of Korea.

²Center for Study of Emerging and Re-emerging Viruses, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea.

³Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.

⁴Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Korea.

†SGJ and YIK contributed equally to this article

Correspondence : Young Ki Choi

Abstract

During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harboring an amino acid substitution from Asparagine(N) to Aspartic acid (D) at residue 193 of the hemagglutinin (HA) receptor binding domain (RBD) from migratory birds in South Korea. Herein, we investigated the characteristics of the N193D HA-RBD substitution in the A/CommonTeal/Korea/W811/2021[CT/W811] virus by using recombinant viruses engineered via reverse genetics (RG). A receptor affinity assay revealed that the N193D HA-RBD substitution in CT/W811 increases α2,6 sialic acid receptor binding affinity. The rCT/W811-HA _193N virus caused rapid lethality with high virus titers in chickens compared with the rCT/W811-HA _193D virus, while the rCT/W811-HA _193D virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA _193D virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA _193N, and all rCT/W811-HA _193D direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA _193D has enhanced growth kinetics compared with the rCT/W811-HA _193N, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA _193D exhibits high infectivity in primary human bronchial epithelial (HBE) cells, suggesting the potential for human infection. Taken together, the HA-193D containing HPAI H5N1 virus from migratory birds showed enhanced virulence in mammalian hosts, but not in avian hosts, with multi-organ replication and ferret-to-ferret transmission. Thus, this suggests that HA-193D change increases the probability of HPAI H5N1 infection and transmission in humans.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-10)
연구진국내 연구진
분야 의약학 > 감염의학

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