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鸡源性禽流感病毒H6N2在人源肺组织细胞中的复制OACSTPCD

Replication of chicken-originated H6N2 subtype avian influenza virus in human lung tissue cells

中文摘要英文摘要

目的:评估鸡源性H6N2亚型禽流感病毒在MDCK、A549和离体人肺中的复制效率,探讨该病毒跨种间屏障感染人的潜能.方法:选取2株鸡源性H6N2禽流感病毒A/CK/HZ/260/2017、A/CK/DG/651/2019,基因测序并分析该2株病毒全基因组的核苷酸同源性及遗传进化,固相直接结合法分析分析病毒的受体结合特异性,应用MDCK、A549和人肺组织评估病毒的复制.结果:鸡源性H6N2病毒基因来源于欧亚谱系,HA、NA均属于GD-SZBJ-like分支,内部基因主要由两个H6N2病毒进化分支的重配进化而来,包括GD-SZBJ-like分支和G1291-like分支,属低致病性禽流感病毒,仅结合禽型受体SAα-2,3Gal,HA的受体结合域未发现向有利于结合人型受体突变.病毒均可在MDCK和A549细胞中复制,离体人肺组织病毒分离培养阳性,免疫组化检测病毒抗原显示,A/CK/HZ/260/2017病毒株在人肺组织和部分细支气管出现流感病毒核蛋白阳性,A/CK/DG/651/2019病毒株在在人肺组织出现流感病毒核蛋白阳性.结论:鸡源性H6N2亚型禽流感病毒仍属低致病性禽流感病毒,仅识别与结合禽型受体,但病毒可不经适应直接在哺乳动物和人下呼吸道进行有效复制,提示鸡源性H6N2禽流感病毒具有跨种属感染人的潜能.

Objective:To assess the replication efficiency of chicken-originated H6N2 subtype avian influenza virus in MDCK,A549 and isolated human lungs,and to explore the potential of the virus crossing inter-species to infect human.Methods:Two strains of chicken-originated H6N2 avian influenza viruses,A/CK/HZ/260/2017 and A/CK/DG/651/2019,were selected for gene sequencing and analysis of nucleotide homology and genetic evo-lution of the full-length genome.The solid-phase direct-binding assay was used to analyze the receptor binding characteristics of the two viruses.MDCK,A549 and the human lung tissues were used to assess the replication of the viruses.Results:The two chicken-originated H6N2 virus genes derived from the Eurasian lineages,both HA and NA came from the GD-SZBJ-like clade,and the internal genes mainly derived from the recombinant virus of two different clades of H6N2,including the GD-SZBJ-like clade and the G1291-like clade.The chicken-originat-ed H6N2 viruses were low pathogenic avian influenza viruses that only bound to the avian receptor SAα-2,3Gal,and no mutation in the receptor binding domain of HA was found to favor the binding of the human-like receptor.Two strains of H6N2 subtype avian influenza viruses can replicate in MDCK and A549 cells.Virus isolation and culture in the isolated human lung tissues were positive.The results of immunohistochemical staining showed that A/CK/HZ/260/2017 virus strain in the human lung tissues and part of bronchioles infected with the HZ260 were positive for influenza viral nucleoprotein,and the A/CK/DG/651/2019 virus strain in the human lung tissues was positive for influenza viral nucleoprotein.Conclusion:The chicken-originated H6N2 subtype avian influen-za virus is still a low pathogenic avian influenza virus,which only recognizes and binds to avian receptors.How-ever,the virus can replicate effectively in mammal and human lower respiratory tissues without adaptation,indi-cating that the chicken-originated H6N2 subtype avian influenza virus has the potential to cross inter-species to infect humans.

何东芳;李周怡;张增峰

广西医科大学基础医学院微生物学教研室,南宁 530021

畜牧业

甲型流感病毒H6N2亚型人肺复制

influenza A virusH6N2 subtypehuman lungreplication

《广西医科大学学报》 2024 (003)

识别与结合人型受体的H6N2、H6N6禽流感病毒在雪貂致病性、传播力以及诱导细胞焦亡的研究

413-418 / 6

国家自然科学基金资助项目(No.32160032)

10.16190/j.cnki.45-1211/r.2024.03.013

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