title: Development of an Attenuated Tat Protein as a Highly-effective Agent to Specifically Activate HIV-1 Latency.
abstract: Although combined antiretroviral therapy (cART) successfully decreases plasma viremia to undetectable levels, the complete eradication of human immunodeficiency virus type 1 (HIV-1) remains impractical because of the existence of a viral reservoir, mainly in resting memory CD4(+) T cells. Various cytokines, protein kinase C activators, and histone deacetylase inhibitors (HDACi) have been used as latency-reversing agents (LRAs), but their unacceptable side effects or low efficiencies limit their clinical use. Here, by a mutation accumulation strategy, we generated an attenuated HIV-1 Tat protein named Tat-R5M4, which has significantly reduced cytotoxicity and immunogenicity, yet retaining potent transactivation and membrane-penetration activity. Combined with HDACi, Tat-R5M4 activates highly genetically diverse and replication-competent viruses from resting CD4(+) T lymphocytes isolated from HIV-1-infected individuals receiving suppressive cART. Thus, Tat-R5M4 has promising potential as a safe, efficient, and specific LRA in HIV-1 treatment.
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Geng
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Cancan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Wu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Junsong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jingliang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiancai
authors.initials: X
authors.lastname: Ma
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ersheng
authors.initials: E
authors.lastname: Kuang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Guangzhou 8th People's Hospital, Guangzhou, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Cai
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D057846:Cell-Penetrating Peptides / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009154:Mutation; D014775:Virus Activation / Q000187:drug effects; D017735:Virus Latency; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D057846:Cell-Penetrating Peptides; D016207:Cytokines; D054322:tat Gene Products, Human Immunodeficiency Virus