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The Per-1 Short Isoform Inhibits de novo HIV-1 Transcription in Resting CD4+ T-cells

[ Vol. 16 , Issue. 6 ]

Author(s):

Li Zhao, Mei Liu, Jiayue Ouyang, Zheming Zhu, Wenqing Geng, Jinxiu Dong, Ying Xiong, Shumei Wang, Xiaowei Zhang, Ying Qiao, Haibo Ding, Hong Sun, Guoxin Liang*, Hong Shang* and Xiaoxu Han*   Pages 384 - 395 ( 12 )

Abstract:


Background: Understanding of the restriction of HIV-1 transcription in resting CD4+ Tcells is critical to find a cure for AIDS. Although many negative factors causing HIV-1 transcription blockage in resting CD4+ T-cells have been found, there are still unknown mechanisms to explore.

Objective: To explore the mechanism for the suppression of de novo HIV-1 transcription in resting CD4+ T-cells.

Methods: In this study, a short isoform of Per-1 expression plasmid was transfected into 293T cells with or without Tat's presence to identify Per-1 as a negative regulator for HIV-1 transcription. Silencing of Per-1 was conducted in resting CD4+ T-cells or monocyte-derived macrophages (MDMs) to evaluate the antiviral activity of Per-1. Additionally, we analyzed the correlation between Per-1 expression and viral loads in vivo, and silenced Per-1 by siRNA technology to investigate the potential anti-HIV-1 roles of Per-1 in vivo in untreated HIV-1-infected individuals.

Results: We found that short isoform Per-1 can restrict HIV-1 replication and Tat ameliorates this inhibitory effect. Silencing of Per-1 could upregulate HIV-1 transcription both in resting CD4+ Tcells and MDMs. Moreover, Per-1 expression is inversely correlated with viral loads in Rapid progressors (RPs) in vivo.

Conclusion: These data together suggest that Per-1 is a novel negative regulator of HIV-1 transcription. This restrictive activity of Per-1 to HIV-1 replication may contribute to HIV-1 latency in resting CD4+ T-cells.

Keywords:

HIV-1, resting CD4+ T-cells, Tat, LTR, viral load, RPs, LTNPs.

Affiliation:

Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, The Core Laboratory for Public Health Science and Practice, The First Affiliated Hospital, China Medical University, Shenyang, The Core Laboratory for Public Health Science and Practice, The First Affiliated Hospital, China Medical University, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang

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