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Virologica Sinica, 33 (3) : 261, 2018
Research Article
HIV-1 Protein Tat1-72 Impairs Neuronal Dendrites via Activation of PP1 and Regulation of the CREB/BDNF Pathway
Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Tianjin 300071, China
 Correspondence: changliu@nankai.edu.cn;kongxh@nankai.edu.cn
(906.86KB)  
Abstract
Despite the success of combined antiretroviral therapy in recent years, the prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders in people living with HIV-1 is increasing, significantly reducing the health-related quality of their lives. Although neurons cannot be infected by HIV-1, shed viral proteins such as transactivator of transcription (Tat) can cause dendritic damage. However, the detailed molecular mechanism of Tat-induced neuronal impairment remains unknown. In this study, we first showed that recombinant Tat (1-72 aa) induced neurotoxicity in primary cultured mouse neurons. Second, exposure to Tat1-72 was shown to reduce the length and number of dendrites in cultured neurons. Third, Tat1-72 (0-6 h) modulates protein phosphatase 1 (PP1) expression and enhances its activity by decreasing the phosphorylation level of PP1 at Thr320. Finally, Tat1-72 (24 h) downregulates CREB activity and CREB-mediated gene (BDNF, c-fos, Egr-1) expression. Together, these findings suggest that Tat1-72 might impair cognitive function by regulating the activity of PP1 and the CREB/BDNF pathway.
Received: 9 Feb 2018  Accepted: 2 Apr 2018  Published online: 8 May 2018
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