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Abstract
The reactivation of HIV latency cell will be necessary to curing HIV infection. Although many latency-reversal agents (LRAs) have proven effective to reactivate the latency cell, there is a lack of any systematic analysis of the molecular targets of these LRAs and related pathways in the context of transcriptome. In this study, we performed an integrated analysis of the target profile of bryostatin and transcriptome of the reactivated CD4+ T cells after exposing to bryostatin. The result showed a distinct gene expression profile between latency cells and bryostatin reactivated cells. We found bryostatin can target multiple types of protein other than only protein kinase C. Functional network analysis of the target profile and differential expressed genes suggested that bryostatin may activate a few novel pathways such as pyrimidine metabolism, purine metabolism and p53 signaling pathway, besides commonly known pathways DNA replication, cell cycle and so on. The results suggest that bryostatin may reactivate the HIV-latent cells through up-regulation of pyrimidine and purine metabolism or through starting the cell-cycle arrest and apoptosis induced by up-regulation of p53 signaling pathway. Our study provides some novel insights into the role of bryostatin and its affected pathways in controlling HIV latency and reactivation.
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Details

1 Peking Union Medical College and Chinese Academy of Medical Sciences, Institute of Medical Biology, Kunming, China
2 Peking Union Medical College and Chinese Academy of Medical Sciences, Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
3 The First Affiliated Hospital of Kunming Medical University, Yunnan Key Laboratory of Laboratory Medicine, Yunnan Institute of Laboratory Diagnosis, Department of Clinical Laboratory, Kunming, China (GRID:grid.414902.a)
4 Kunming Institute of Zoology, Chinese Academy of Sciences, State Key Laboratory of Genetic Resources and Evolution, Kunming, China (GRID:grid.419010.d) (ISNI:0000 0004 1792 7072)
5 Peking Union Medical College and Chinese Academy of Medical Sciences, Institute of Medical Biology, Kunming, China (GRID:grid.419010.d)
6 Kunming University of Science and Technology, Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming, China (GRID:grid.218292.2) (ISNI:0000 0000 8571 108X)