title: Progress and challenges in the use of latent HIV-1 reactivating agents.
abstract: Highly active antiretroviral therapy (HAART) can effectively suppress the replication of human immunodeficiency 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-1-infected patients. This review comprehensively summarizes the recent progress and relative challenges in this field.
authors.affiliation: Department of Medical Engineering, General Hospital of Beijing Military Area Command of PLA, Beijing 100700, China.
authors.forename: Hong-tao
authors.initials: HT
authors.lastname: Shang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Ji-wei
authors.initials: JW
authors.lastname: Ding
authors.affiliation: Department of Medical Engineering, General Hospital of Beijing Military Area Command of PLA, Beijing 100700, China.
authors.forename: Shu-ying
authors.initials: SY
authors.lastname: Yu
authors.affiliation: Department of Medical Engineering, General Hospital of Beijing Military Area Command of PLA, Beijing 100700, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Medical Engineering, General Hospital of Beijing Military Area Command of PLA, Beijing 100700, China.
authors.forename: Qiu-li
authors.initials: QL
authors.lastname: Zhang
authors.affiliation: Center of Infectious Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Fu-jun
authors.initials: FJ
authors.lastname: Liang
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D016207:Cytokines / Q000494:pharmacology / Q000627:therapeutic use; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors; D006801:Humans; D017735:Virus Latency / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D015254:DNA Modification Methylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase