期刊
MOLECULAR THERAPY
卷 24, 期 9, 页码 1528-1537出版社
CELL PRESS
DOI: 10.1038/mt.2016.117
关键词
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资金
- National Special Research Program for Important Infectious Diseases [2013ZX10001004, 2012ZX10001003-004-002]
- Introduction of Innovative R&D Team Program of Guangdong Province [2009010058]
- International Collaboration Program of Natural Science Foundation of China [81561128007]
- Important Key Program of Natural Science Foundation of China [81590765]
- Joint-innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou [201508020256]
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.
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