Impact of HIV-1 Tat on FDFT1 Suppression, Changes in Cholesterol Level, and KSHV Replication in BCBL1 Cells.

IF 1 4区医学 Q4 IMMUNOLOGY

Current HIV Research Pub Date : 2025-09-11 DOI:10.2174/011570162X371221250630105858

Qiaozhen Liu, Xiaoying Chen, Dewen Liu, Yuting Zou, Weiling Yang, Ziyi Cao, Yao Ding, Weihang Ji, Na Xiao, Huaying Tang, Yan Jiang, Liandeng Wei, Yi Zeng

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引用次数: 0

Abstract

Introduction: The present study investigated the molecular mechanism by which the transactivator of transcription (Tat) protein of Human Immunodeficiency Virus 1 (HIV-1) activates the replication cycle of Kaposi's Sarcoma-associated Herpesvirus (KSHV).

Methods: BCBL-1 cells were initially infected with lentivirus overexpressing HIV-1 Tat. The relative mRNA expression of Farnesyl Diphosphate Farnesyltransferase 1 (FDFT1), HIV-1 Tat, KSHV Open Reading Frame 73 (ORF73), and KSHV Open Reading Frame 50 (ORF50) was quantified by real-time fluorescent quantitative Polymerase Chain Reaction (RT-qPCR). The cellular cholesterol levels were determined using a total cholesterol assay kit. BCBL-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) served as a positive control for the lytic replication of KSHV. The relative mRNA expression levels of HIV-1 Tat, FDFT1, KSHV ORF73, and KSHV ORF50 were subsequently evaluated in BCBL-1 cells following infection with lenti-viruses for FDFT1 overexpression or FDFT1-RNAi knockdown, and the cellular cholesterol content was quantified.

Results: The findings revealed that HIV-1 Tat downregulated FDFT1 and upregulated the expression of KSHV ORF50 in BCBL-1 cells. FDFT1 overexpression upregulated the expression of the latency-associated gene, ORF73, of KSHV in BCBL-1 cells, while knockdown of FDFT1 upregulated the expression of genes associated with the lytic reactivation of KSHV. Infection with the HIV-1 lentivirus, which overexpresses Tat, as well as manipulation of FDFT1, significantly altered the cholesterol content in BCBL-1 cells.

Conclusion: The downregulation of FDFT1 by HIV-1 Tat modulates cellular cholesterol levels and is associated with KSHV replication in BCBL-1 cells.

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HIV-1 Tat对BCBL1细胞中FDFT1抑制、胆固醇水平变化和KSHV复制的影响

本研究探讨了人类免疫缺陷病毒1号（HIV-1）转录反激活因子（Tat）蛋白激活卡波西肉瘤相关疱疹病毒（KSHV）复制周期的分子机制。方法：先用过表达HIV-1 Tat的慢病毒感染BCBL-1细胞。采用实时荧光定量聚合酶链式反应（RT-qPCR）检测法尼基二磷酸法尼基转移酶1 （FDFT1）、HIV-1 Tat、KSHV开放阅读框73 （ORF73）、KSHV开放阅读框50 (ORF50) mRNA的相对表达量。用总胆固醇测定试剂盒测定细胞胆固醇水平。12- o - tetradecanoylphorol -13-acetate （TPA）处理的bccl -1细胞作为KSHV裂解复制的阳性对照。在慢病毒感染bbcl -1细胞后，检测FDFT1过表达或FDFT1- rnai敲低后，HIV-1 Tat、FDFT1、KSHV ORF73和KSHV ORF50 mRNA的相对表达水平，并定量测定细胞胆固醇含量。结果：在bccl -1细胞中，HIV-1 Tat下调FDFT1，上调KSHV ORF50的表达。FDFT1过表达可上调bcl -1细胞中KSHV潜伏期相关基因ORF73的表达，而FDFT1敲低可上调KSHV裂解再激活相关基因的表达。感染过表达Tat的HIV-1慢病毒，以及操纵FDFT1，显著改变了bccl -1细胞中的胆固醇含量。结论：HIV-1 Tat对FDFT1的下调可调节细胞胆固醇水平，并与bccl -1细胞中的KSHV复制有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current HIV Research 医学-病毒学

CiteScore

1.90

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Current HIV Research covers all the latest and outstanding developments of HIV research by publishing original research, review articles and guest edited thematic issues. The novel pioneering work in the basic and clinical fields on all areas of HIV research covers: virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Periodically, the journal invites guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.