Antiretroviral therapy(ART)can effectively inhibit human immunodeficiency virus-1(HIV-1)replication,but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruse...Antiretroviral therapy(ART)can effectively inhibit human immunodeficiency virus-1(HIV-1)replication,but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruses.In order to reduce or eliminate the HIV-1 latent reservoir,characteristics of the latently infected cells need to be intensively studied,and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic strategies.Here,we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs,and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome(AIDS).展开更多
艾滋病(AIDS)是由人类免疫缺陷病毒(HIV)引起的获得性机体免疫缺陷综合征。高效抗反转录病毒治疗是目前治疗AIDS患者最有效的方法,其虽可降低病人体内病毒载量,但却不能彻底清除病毒。2012年“shock and kill”治疗策略被提出,该策略利...艾滋病(AIDS)是由人类免疫缺陷病毒(HIV)引起的获得性机体免疫缺陷综合征。高效抗反转录病毒治疗是目前治疗AIDS患者最有效的方法,其虽可降低病人体内病毒载量,但却不能彻底清除病毒。2012年“shock and kill”治疗策略被提出,该策略利用HIV潜伏激活剂(LRA)激活潜伏在CD4+T细胞内的HIV-1使其暴露,随后通过增强免疫系统或采用抗病毒药物消灭携带有病毒的宿主细胞,从而逐渐清除病毒潜伏库,最终实现艾滋病的功能性治愈。HIV-1潜伏机制主要有5种:表观遗传学调控、转录因子对基因的调控、免疫信号通路的调节、前病毒基因整合位点的影响和微RNA的影响。基于HIV-1的潜伏机制,目前有潜力作为LRA的药物主要包括表观遗传修饰剂、转录因子调节剂和免疫激活剂等。本文对以上几类药物的作用机制、代表性药物以及研究进展进行综述,以期为LRA研发提供思路。展开更多
Objective： To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. Data Sources： Literatures related to the size of HIV DNA was collecte...Objective： To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. Data Sources： Literatures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016. Study Selection： All relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design. Results： The composition and development of the HIV- 1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies. The HIV DNA reservoir is a combination of latency and activity. The residual viremia from the stochastic activation of the reservoir acts as the fuse, continuing to stimulate the immune system to maintain the activated microenvironment for the rebound of competent virus once treatment with antiretroviral therapy is discontinued. Conclusion： The size of the HIV-1 DNA pool and its composition has great significance in clinical treatment and disease progression.展开更多
基金This work was supported by grants from the National Special Research Program of China for Important Infectious Diseases(No.2018ZX10302103 and No.2017ZX10202102)National Natural Science Foundation of China(No.81672024)+1 种基金Natural Science Foundation of Guangdong Province of China(No.2017A030306005)Guangdong Innovative and Entrepreneurial Research Team Program(No.2016ZT06S638)。
文摘Antiretroviral therapy(ART)can effectively inhibit human immunodeficiency virus-1(HIV-1)replication,but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruses.In order to reduce or eliminate the HIV-1 latent reservoir,characteristics of the latently infected cells need to be intensively studied,and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic strategies.Here,we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs,and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome(AIDS).
文摘艾滋病(AIDS)是由人类免疫缺陷病毒(HIV)引起的获得性机体免疫缺陷综合征。高效抗反转录病毒治疗是目前治疗AIDS患者最有效的方法,其虽可降低病人体内病毒载量,但却不能彻底清除病毒。2012年“shock and kill”治疗策略被提出,该策略利用HIV潜伏激活剂(LRA)激活潜伏在CD4+T细胞内的HIV-1使其暴露,随后通过增强免疫系统或采用抗病毒药物消灭携带有病毒的宿主细胞,从而逐渐清除病毒潜伏库,最终实现艾滋病的功能性治愈。HIV-1潜伏机制主要有5种:表观遗传学调控、转录因子对基因的调控、免疫信号通路的调节、前病毒基因整合位点的影响和微RNA的影响。基于HIV-1的潜伏机制,目前有潜力作为LRA的药物主要包括表观遗传修饰剂、转录因子调节剂和免疫激活剂等。本文对以上几类药物的作用机制、代表性药物以及研究进展进行综述,以期为LRA研发提供思路。
文摘Objective： To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. Data Sources： Literatures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016. Study Selection： All relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design. Results： The composition and development of the HIV- 1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies. The HIV DNA reservoir is a combination of latency and activity. The residual viremia from the stochastic activation of the reservoir acts as the fuse, continuing to stimulate the immune system to maintain the activated microenvironment for the rebound of competent virus once treatment with antiretroviral therapy is discontinued. Conclusion： The size of the HIV-1 DNA pool and its composition has great significance in clinical treatment and disease progression.
