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

• Published in: Current HIV research Vol. 16; no. 6; p. 384
• Main Authors: Zhao, Li, Liu, Mei, Ouyang, Jiayue, Zhu, Zheming, Geng, Wenqing, Dong, Jinxiu, Xiong, Ying, Wang, Shumei, Zhang, Xiaowei, Qiao, Ying, Ding, Haibo, Sun, Hong, Liang, Guoxin, Shang, Hong, Han, Xiaoxu
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2018
• Subjects: CD4-Positive T-Lymphocytes - virology; Cell Line; Gene Silencing; HIV Infections - virology; HIV-1 - growth & development; HIV-1 - immunology; Host-Pathogen Interactions; Humans; Immunologic Factors - genetics; Immunologic Factors - metabolism; Monocytes - virology; Period Circadian Proteins - genetics; Period Circadian Proteins - metabolism; Transcription, Genetic; Viral Load; Virus Replication; HIV-1; viral load; RPs; Tat; resting CD4+ T-cells; LTR; LTNPs
• ISSN: 1873-4251
• DOI: 10.2174/1570162X17666190218145048

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