title: Toll-interacting protein inhibits HIV-1 infection and regulates viral latency.
abstract: HIV-1 latency is mainly characterized by a reversible silencing of long-terminal repeat (LTR)-driven transcription of provirus. The existing of repressive factors has been described to contribute to transcription silencing of HIV-1. Toll-interacting protein (Tollip) has been identified as a repressor of Toll like receptors (TLR)-mediated signaling. Our previous study has found that Tollip inhibited NF-κB-dependent HIV-1 promoter LTR-driven transcription, indicating the potential role of Tollip in governing viral latency. In this study, by using HIV-1 latently infected Jurkat T-cell and central memory CD4(+) T-cells, we demonstrate the role of Tollip in regulating HIV-1 latency, as the knock-down of Tollip promoted HIV-1 reactivation from both HIV-1 latently infected Jurkat CD4(+) T cells and primary central memory T cells (TCM). Moreover, we found that the activities of LTRs derived from multiple HIV-1 subtypes could be repressed by Tollip; Knock-down of Tollip promoted HIV-1 transcription and infection in CD4(+) T cells. Our data indicate a key role of Tollip in suppressing HIV-1 infection and regulating viral latency, which provides a potential host target for combating HIV-1 infection and latency.
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wen-Dong
authors.initials: WD
authors.lastname: Kuang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China. Electronic address: jh_wang@sibs.ac.cn.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017735:Virus Latency
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C410602:TOLLIP protein, human
keywords: HIV-1; Long-terminal repeat; Toll-interacting protein; Viral latency