PLoS One:中科院上海巴斯德所金侠研究组发表丙型肝炎病毒T细胞反应研究成果

2017-02-15 佚名 生物帮

2017年2月7日,国际知名学术期刊《PLOS ONE》在线发表了中国科学院上海巴斯德研究所金侠研究组和吉林大学第一医院牛俊奇研究组合作的最新研究成果



2017年2月7日,国际知名学术期刊《PLoS ONE》在线发表了中国科学院上海巴斯德研究所金侠研究组和吉林大学第一医院牛俊奇研究组合作的最新研究成果,题为“Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance”。研究系统地鉴定了丙型肝炎病毒1b亚型(HCV-1b)特异性T细胞表位,为后续疫苗开发奠定了基础。博士研究生张超为论文第一作者,金侠研究员为论文通讯作者。

HCV感染是全球慢性肝炎的主要病因之一,全球约有1.8亿慢性HCV感染病例,每年约50万人死于HCV相关疾病。在我国,HCV感染率约为3.2%。HCV感染人体之后,约15%的感染者能不经治疗而自发恢复,约85%则转为慢性感染,并在感染后期引起肝硬化、肝癌等严重疾病。目前在中国针对HCV感染主要的治疗方式为聚乙二醇干扰素联合利巴韦林,其治愈率只有约50%。新一代药物Direct-antiviral agents (DAAs)虽然能将治愈率提高到90%以上,但在中国仍未上市,且价格昂贵,也存在产生耐药的可能。而目前仍未有针对HCV的预防性疫苗上市。早期研究发现,在自发恢复的病人体内,HCV特异性T细胞反应更强,更广谱,T细胞功能更强,记忆性T细胞更容易产生。而在慢性感染病人体内,HCV特异性T细胞反应则相对较弱,表现为低水平的白介素-2(IL-2)表达、弱细胞增殖能力、高PD-1分子表达等。因此,我们假设自发恢复的HCV感染病人体内的T细胞反应将为研究HCV保护性免疫提供线索,且DAA治疗有可能影响慢性病人体内HCV特异性T细胞反应。

研究组设计并合成了376条覆盖HCV-1b亚型全长的重叠多肽序列,并在吉林大学第一医院和北京佑安医院收集了111例HCV-1b感染病例样本,包括61例HCV-1b慢性感染、24例HCV-2a慢性感染和26例自发恢复。基于IFN-γ Elispot试验对所有样本进行T细胞表位鉴定。结果表明,自发恢复病人比慢性感染病人T细胞反应更强,更广谱。鉴定出39个特异性T细胞表位,主要分布在HCV的Core、E1、E2、NS4B、NS5A区域,且包含了23个新表位。进而收集了22例DAA临床治疗过程中的HCV-1b慢性感染病人样本,研究DAA治疗过程中HCV特异性T细胞反应的变化。结果发现尽管DAA能够在治疗早期就有效地清除慢性感染病人血液中的病毒,但是并没有导致早期的HCV特异性T细胞功能的恢复。因此,长期的慢性感染有可能导致了HCV特异性T细胞反应的耗竭,针对HCV感染的尽早治疗是有必要的。

PLoS One:中科院上海巴斯德所金侠研究组发表丙型肝炎病毒T细胞反应研究成果


图 自发恢复病人比慢性感染病人具有更强的特异性t细胞反应

慢性HCV感染(HCC);自发恢复(SPR)。A. 样本T细胞反应率;B. 总T细胞反应强度;C. T细胞多肽反应数;D. 各蛋白T细胞反应打分。E. 单挑多肽T细胞反应平均分数。F. HCV-1b和HCV-2a一致序列相似性比较。

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    2017-10-18 gous
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    2017-02-15 Albert Wu

    很好,不错,以后会多学习

    0

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    2017-02-15 李东泽

    很好,不错,以后会多学习

    0

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    2017-02-15 1e145228m78(暂无匿称)

    学习了,不太实用,但开拓视野

    0

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