人感染新型H10N3禽流感病毒分子溯源

Molecular origion of human infection with a novel avian influenza A H10N3 virus in China, 2021

摘要:

【背景】1997年香港发生人感染禽流感事件以来，禽流感病毒成为持续威胁人类健康和公共卫生的重要病原体。【目的】对一例人感染新型H10N3禽流感病毒病例开展分子溯源研究。【方法】流感病毒分型检测采用RT-qPCR法，在下一代测序平台上完成病毒基因组测序，序列和系统进化分析采用BLAST和MEGA 6.1等生物信息学软件。【结果】2021年4月从严重呼吸道疾病患者体内分离到一株病毒，经核酸检测和序列分析，结果表明其为H10N3亚型禽流感病毒。从患者居所附近的农贸市场分离到一株基因高度同源的H10N3亚型禽流感病毒。分离株是一种新的基因重配H10N3禽流感病毒，其血凝素hemagglutinin (HA)和神经氨酸酶neuraminidase (NA)组合最早在2019年华东地区的家禽中检测到，6个内部基因来源于近年来中国南方家禽中流行的H9N2病毒。病毒的HA蛋白的裂解位点含有1个碱性氨基酸R，未插入多个碱性氨基酸，理论上不属于高致病性禽流感病毒。HA蛋白受体结合位点228位氨基酸残基由G突变为S，理论上增强了对人SAα2,6受体的亲和力。另外，未发现PB2蛋白E627K突变，但591位氨基酸残基由Q突变为K，理论上增强了对人体的适应力和致病性。【结论】本研究报道了一例人感染H10N3禽流感病毒病例的分子流行病学特征，揭示了活禽市场在禽流感病毒基因重配和机会性外溢感染人过程中起重要作用。

关键词:禽流感病毒;H10N3亚型;人感染

Abstract:

[Background] Since the human infection with avian influenza that occurred in Hong Kong in 1997, avian influenza virus has become a major threat to human health and public health. [Objective] To perform the molecular epidemiological study on a human infection with H10N3 avian influenza. [Methods] Influenza virus subtyping was detected by real-time quantitative polymerase chain reaction (PCR) method. The virus genome sequencing was completed on the next-generation sequencing platform. Bioinformatics software such as Blasts and Mega 6.1 was used for sequence and phylogenetic analysis. [Results] In April 2021, a virus was isolated from patients with severe respiratory diseases, which was confirmed as H10N3 subtype avian influenza virus by nucleic acid detection and sequence analysis. A H10N3 subtype avian influenza virus was isolated from the farm product market near the patient’s residence, which was highly homologous with the human isolate. The human isolate was a new gene recombinant H10N3 avian influenza virus, and its HA and NA combination first appeared in poultry in East China in 2019. However, its six internal genes came from H9N2 virus prevalent in poultry in southern China in recent years. The HA cleavage site of the virus contained one basic amino acid R, without insertion of multiple basic amino acids. In theory, it did not belong to highly pathogenic avian influenza virus. The amino acid residue at 228 of HA receptor binding site mutated from G to S, which theoretically enhanced the affinity with human SA-α-2,6 receptor. No E627K mutation of PB2 protein was found, but the amino acid residue at site 591 mutated from Q to K, which theoretically enhanced the adaptability to human body and the pathogenicity. [Conclusion] This paper reported the molecular epidemiological characteristics of a case of human infection with H10N3 avian influenza virus, and revealed that live poultry market played an important role in gene recombination of avian influenza virus and opportunistic infection.

Key words:avian influenza A virus;H10N3 subtype;human infection