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Mechanisms of HIV envelope-induced T lymphocyte apoptosis

Virologica Sinica 2010年第5期25卷 307-315页

作者： Zhi-Tao WAN Xu-lin CHEN State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071China

Infection by the human immunodeficiency virus （HIV） is characterized by a progressive depletion of CD4 T lymphocytes, which leads to dysfunction of the immune system. Although a variety of mechanisms may contribute to the gradual T cell decline that occurs in H/V-infected patients, abnormal apoptosis of infected or bystander T lymphocytes is an important event leading to immunodeficiency. The HIV envelope glycoprotein plays a crucial role in HIV associated apoptosis through both death receptor-mediated and mitochondria-dependent pathways. This review summarizes current knowledge of Env-mediated T lymphocyte apoptosis.

关键词： HIV envelope glycoprotein T lymphocyte Apoptosis

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Cross-Subtype Neutralizing Antibodies in Treatmentnaive HIV-1-infected Individuals in China and characteristics of viral envelope derived from broad neutralizers

Cross-Subtype Neutralizing Antibodies in Treatmentnaive HIV-...

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第八届全国免疫学学术大会

作者： Hong Ling Ping Zhong Caiyun Ren Song Liu Yan Li Haotong Yu Min Zhuang Guochao Wei Jiaye Wang Zhijie Chen Feng Sun Wei Liu Shujia Liang Harbin Medical University Shanghai Municipal Center for Disease Control and Prevention Yili Prefecture CDC Guangxi CDC

Background:Little is known about breadth of neutralizing antibody(NAb) responses and the viral envelope characterization in Chinese treatment-nave ***:To clarify the profile of NAb from broad HIV-1 neutralizers and find potential ***:866 plasma samples from antiretroviral treatment-nave HIV-1-infected individuals, who mostly had acquired infection over 3 years through injecting drug use(IDU) and sexual contact, living in Xinjiang province(617) and Guangxi province(249) were analyzed for their ability to neutralize diverse pseudoviruses using the TZM-b1 pseudovirus *** NAb breadth was evaluated based on both number of viruses neutralized and neutralization *** genome amplification(SGA) of envelope genes and sequencing were performed to identify the sequence characteristics of the envelope glycoproteins from broad ***:We have found that for Xingjiang province, where most samples were derived from IDUs, 20 of 617(3.2%) plasma neutralized all of four subtype B and 39(5.3%) neutralized all of four subtype C at virus inhibition >80%.Only 10(1.6%) and 5(0.8%) plasma were able to neutralize the viruses of both subtype, B and C.5(0.8%) plasma were able to neutralize all 11 viruses of three different subtypes, B, C, and CRF01E at virus inhibition >80%.However, for Guangxi province where most samples were derived from sexual contact infection, lower neutralization titers were found with same virus *** variations of viral envelope glycoproteins between broad and non-broad neutralizers showed some unique ***:The breadth and potency of Nab against diverse HIV-1 subtypes in Chinese HIV-1-infected individuals was clarified for the first time.

关键词： HIV-1 neutralization antibody envelope glycoprotein broad neutralizers

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Cross-subtype neutralizing antibodies in treatment-naive HI V-1 -infected individuals in China and characteristics of viral envelope derived from broad neutralizes

Cross-subtype neutralizing antibodies in treatment-naive HI ...

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2012全国临床微生物与感染免疫学术研讨会

作者： Ling Hong~1,Zhong Ping~3,Ren Caiyun~1,Liu Song~1,Li Yan~1,Yu Haotong~1,Zhuang Min~1,Wei Guochao~1, Wang Jiaye~1,Chen Zhijie~3,Sun Feng~3,Liu Wei~4,Liang Shujia~4 1.Harbin Medical University,Heilongjiang province 2.Shanghai Municipal Center for Disease Control and Prevention,Shangha 3.Yili Prefecture CDC,Xinjinag province 4.Guangxi CDC,Guangxi province

Background Little is known about breadth of neutralizing antibody(NAb) responses and the viral envelope characterization in Chinese treatment-naive individuals. Objectives To clarify the profile of NAb from broad HIV-1 neutralizers and to find potential immunogen. Methods 866 plasma samples from antiretroviral treatment-naive HIV-1-infected individuals,who mostly had acquired infection over 3 years through injecting drug use(IDU) and sexual contact,living in Xinjiang province (617) and Guangxi province(249) were analyzed for their ability to neutralize diverse pseudoviruses using the TZM-b1 pseudovirus *** NAb breadth was evaluated based on both number of viruses neutralized and neutralization *** genome amplification(SGA) of envelope genes and sequencing were performed to identify the sequence characteristics of the envelope glycoproteins from broad neutralizers. Results We have found that in Xingjiang province,where most samples were derived from IDUs,20 of 617 (3.2%) plasma neutralized all of four subtype B and 39(5.3%) neutralized all of four subtype C at virus inhibition>80%.Only 10(1.6%) and 5(0.8%) plasma were able to neutralize the viruses of both subtype B and C.5 (0.8%) plasma were able to neutralize all 11 viruses of three different subtypes B,C,and CRF01E at virus inhibition>80%.However,in Guangxi province where most samples were derived from sexual contact infection, lower neutralization titers were found with the same virus *** variations of viral envelope glycoproteins between broad and non-broad neutralizers showed some unique characteristics. Conclusions The breadth and potency of Nab against diverse HIV-1 subtypes in Chinese HIV-1-infected individuals was clarified for the first time.

关键词： HIV-1 Neutralization antibody envelope glycoprotein Broad neutralizers

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丙型肝炎病毒的包膜糖蛋白糖基化突变体及其中和性单克隆抗体作为治疗性HCV候选疫苗

丙型肝炎病毒的包膜糖蛋白糖基化突变体及其中和性单克隆抗体作为...

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第九届全国免疫学学术大会

作者：章晓联任玉珊闵远琴林苗武汉大学基础医学院免疫学系病毒学国家重点实验室湖北省过敏及免疫相关疾病重点实验室

背景:丙型肝炎病毒(Hepatitis C Virus,HCV)是导致肝细胞疾病的重要病毒,目前尚无有效疫苗。HCV包膜糖蛋白E1-E2的免疫原性弱,E1E2上含有丰富的N-糖基化修饰的糖链,研究显示糖链可能遮盖病毒抗原表位,从而抑制和影响病毒的免疫原性,导... 详细信息

背景:丙型肝炎病毒(Hepatitis C Virus,HCV)是导致肝细胞疾病的重要病毒,目前尚无有效疫苗。HCV包膜糖蛋白E1-E2的免疫原性弱,E1E2上含有丰富的N-糖基化修饰的糖链,研究显示糖链可能遮盖病毒抗原表位,从而抑制和影响病毒的免疫原性,导致病毒免疫逃逸。目的:本研究拟改造E1E2的N-糖链,筛选出能比野生型的免疫原性增强的糖基化突变体;并通过B细胞表面的CD19分子将HCV-E2靶向递呈到B细胞,研究这种靶向性抗原是否能够通过激活B细胞诱导丙肝特异性中和抗体和细胞毒性T细胞免疫反应,为研制新型免疫原性增强的治疗性HCV疫苗提供新的策略。结果:1.筛选获得两个HCV包膜糖蛋白N-糖基化突变体,其能诱导比野生型更强且最强的中和性抗体水平和细胞免疫应答;并且用糖基化突变体制备的单克隆抗体能显著抑制HCVcc感染Huh7.5.1细胞。2.构建的sE2-scFV融合蛋白能够将sE2抗原靶向B细胞,并改善E2蛋白的弱免疫原性,可作为B细胞靶向性HCV疫苗,增强抗HCV免疫保护反应。sE2-scFV制备的单克隆抗体能显著抑制HCVcc感染Huh7.5.1细胞。结论:获得两个HCV包膜糖蛋白N-糖基化突变体均诱导显著的中和性抗体水平和细胞免疫应答,均可以能作为新型的免疫原性增强的HCV候选治疗性疫苗。获得的HCV包膜糖蛋白N-糖基化突变体的单抗能显著抑制和中和HCV病毒颗粒的感染,具有作为治疗性中和性抗体的潜在应用价值。

关键词： HCV Vaccine envelope glycoprotein N-glycosylation therapeutic vaccine

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