Seung-Gyu Jang, Young-Il Kim, Mark Anthony B Casel, Jeong Ho Choi, Ju Ryeon Gil, Rare Rollon, Eun-Ha Kim, Se-Mi Kim, Ho Young Ji, Dong Bin Park, Jungwon Hwang, Jae-Woo Ahn, Myung Hee Kim, Min-Suk Song, Young Ki Choi
{"title":"高致病性禽流感 H5N1 病毒中的 HA N193D 置换改变了受体结合亲和力并增强了对哺乳动物宿主的毒力。","authors":"Seung-Gyu Jang, Young-Il Kim, Mark Anthony B Casel, Jeong Ho Choi, Ju Ryeon Gil, Rare Rollon, Eun-Ha Kim, Se-Mi Kim, Ho Young Ji, Dong Bin Park, Jungwon Hwang, Jae-Woo Ahn, Myung Hee Kim, Min-Suk Song, Young Ki Choi","doi":"10.1080/22221751.2024.2302854","DOIUrl":null,"url":null,"abstract":"<p><p>During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring 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<sub>193N</sub> virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA<sub>193D</sub> virus, while the rCT/W811-HA<sub>193D</sub> virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA<sub>193D</sub> virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA<sub>193N</sub>, and all rCT/W811-HA<sub>193D</sub> direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA<sub>193D</sub> has enhanced growth kinetics compared with the rCT/W811-HA<sub>193N</sub>, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA<sub>193D</sub> 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.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2302854"},"PeriodicalIF":8.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840603/pdf/","citationCount":"0","resultStr":"{\"title\":\"HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts.\",\"authors\":\"Seung-Gyu Jang, Young-Il Kim, Mark Anthony B Casel, Jeong Ho Choi, Ju Ryeon Gil, Rare Rollon, Eun-Ha Kim, Se-Mi Kim, Ho Young Ji, Dong Bin Park, Jungwon Hwang, Jae-Woo Ahn, Myung Hee Kim, Min-Suk Song, Young Ki Choi\",\"doi\":\"10.1080/22221751.2024.2302854\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring 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<sub>193N</sub> virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA<sub>193D</sub> virus, while the rCT/W811-HA<sub>193D</sub> virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA<sub>193D</sub> virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA<sub>193N</sub>, and all rCT/W811-HA<sub>193D</sub> direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA<sub>193D</sub> has enhanced growth kinetics compared with the rCT/W811-HA<sub>193N</sub>, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA<sub>193D</sub> 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.</p>\",\"PeriodicalId\":11602,\"journal\":{\"name\":\"Emerging Microbes & Infections\",\"volume\":\" \",\"pages\":\"2302854\"},\"PeriodicalIF\":8.4000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840603/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Emerging Microbes & Infections\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/22221751.2024.2302854\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Emerging Microbes & Infections","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/22221751.2024.2302854","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts.
During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring 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-HA193N virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA193D virus, while the rCT/W811-HA193D virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA193D virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA193N, and all rCT/W811-HA193D direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA193D has enhanced growth kinetics compared with the rCT/W811-HA193N, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA193D 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.
期刊介绍：
Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses.
The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries.
This journal addresses topics of critical biological and clinical importance, including but not limited to:
- Epidemic surveillance
- Clinical manifestations
- Diagnosis and management
- Cellular and molecular pathogenesis
- Innate and acquired immune responses between emerging microbes and their hosts
- Drug discovery
- Vaccine development research
Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.
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