Progress and challenges in the use of latent HIV-1 reactivating agents  

作　　者：Hong-tao SHANG Ji-wei DING Shu-ying YU Tao WU Qiu-li ZHANG Fu-jun LIANG 

机构地区：[1]Department of Medical Engineering, General Hospital of Beijing Military Area Command of PLA, Beijing 100700, China [2]Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China [3]Center of Infectious Disease, Beijing 302 Hospital, Beijing 100039, China

出　　处：《Acta Pharmacologica Sinica》2015年第8期908-916,共9页中国药理学报（英文版）

摘　　要：Highly active antiretroviral therapy （HAART） can effectively suppress the replication of human immunodeflciency virus-1 （HIV-1） and block disease progression. However, chronic HIV-1 infection remains incurable due to the persistence of a viral reservoir, including the transcriptionally silent provirus in CD4＋ memory T cells and the sanctuary sites that are inaccessible to drugs. Reactivation and the subsequent elimination of latent virus through virus-specific cytotoxic effects or host immune responses are critical strategies for combating the disease. Indeed, a number of latency reactivating reagents have been identified through mechanism-directed approaches and large-scale screening, including： （1） histone deacetylase inhibitors （HDACi）; （2） cytokines and chemokines; （3） DNA methyltransferase inhibitors （DNMTI）; （4） histone methyltransferase inhibitors （HMTI）; （5） protein kinase C （PKC） activators; （6） P-TEFb activators; and （7） unclassified agents, such as disulfram. They have proved to be efficacious in latent cell line models and CD4＊ T lymphocytes from HIV-l-infected patients. This review comprehensively summarizes the recent progress and relative challenges in this field.Highly active antiretroviral therapy （HAART） can effectively suppress the replication of human immunodeflciency virus-1 （HIV-1） and block disease progression. However, chronic HIV-1 infection remains incurable due to the persistence of a viral reservoir, including the transcriptionally silent provirus in CD4＋ memory T cells and the sanctuary sites that are inaccessible to drugs. Reactivation and the subsequent elimination of latent virus through virus-specific cytotoxic effects or host immune responses are critical strategies for combating the disease. Indeed, a number of latency reactivating reagents have been identified through mechanism-directed approaches and large-scale screening, including： （1） histone deacetylase inhibitors （HDACi）; （2） cytokines and chemokines; （3） DNA methyltransferase inhibitors （DNMTI）; （4） histone methyltransferase inhibitors （HMTI）; （5） protein kinase C （PKC） activators; （6） P-TEFb activators; and （7） unclassified agents, such as disulfram. They have proved to be efficacious in latent cell line models and CD4＊ T lymphocytes from HIV-l-infected patients. This review comprehensively summarizes the recent progress and relative challenges in this field.

关 键 词：HIV infection virus latency HIV reactivating agents INTERLEUKIN-7 disulfram protein kinase C agonist histone deacetylase inhibitors DNA methyltranserase inhibitors ＂shock and kill＂ strategy CD4-positive T-lymphocytes 

分 类 号：Q78[生物学—分子生物学] TN104.3[电子电信—物理电子学]