Two cellular microRNAs, miR-196b and miR-1290, contribute to HIV-1 latency

Wang, Pengfei; Qu, Xin; Zhou, Xin; Shen, Yinzhong; Ji, Haiyan; Fu, Zheng; Deng, Jixin; Lu, Panpan; Yu, Wenbo; Lu, Hongzhou; Zhu, Hengrui

doi:10.1016/j.virol.2015.09.016

Cited by 39 publications

(27 citation statements)

References 63 publications

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“…YA cells and C11 cells, which are HIV-1-infected or latently infected Jurkat T cells, respectively, were first created in our laboratory and are now used widely in the research community 36, 37, 51, 52, 53, 54. The C11 and YA cells were maintained in RPMI 1640 medium supplemented with 10% (v/v) fetal bovine serum (Gibco), 100 U mL −1 penicillin, and 100 μg mL −1 streptomycin (Invitrogen) at 37°C under 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1

Deng

et al. 2017

Molecular Therapy - Nucleic Acids

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HIV-1 inserts its proviral DNA into the infected host cells, by which HIV proviral DNA can then be duplicated along with each cell division. Thus, provirus cannot be eradicated completely by current antiretroviral therapy. We have developed an innovative strategy to silence the HIV provirus by targeted DNA methylation on the HIV promoter region. We genetically engineered a chimeric DNA methyltransferase 1 composed of designed zinc-finger proteins to become ZF2 DNMT1. After transient transfection of the molecular clone encoding this chimeric protein into HIV-1 infected or latently infected cells, efficient suppression of HIV-1 expression by the methylation of CpG islands in 5′-LTR was observed and quantified. The effective suppression of HIV in latently infected cells by ZF2-DNMT1 is stable and can last through about 40 cell passages. Cytotoxic caused by ZF2-DNMT1 was only observed during cellular proliferation. Taken together, our results demonstrate the potential of this novel approach for anti-HIV-1 therapy.

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Section: Methodsmentioning

confidence: 99%

Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1

Deng

et al. 2017

Molecular Therapy - Nucleic Acids

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“…In contrast, Whisnant et al (2013) [ 222 ] tested the primary CD4 + PBMCs 3 days post infection, because, as they reason in their report, the HIV-1-infected T cells in vivo have a half-life of only around 24 h [ 227 ]. By comparing the miRNA expression profiles of cells productively or latently infected by HIV-1, Wang et al [ 224 ] identified two cellular miRNAs- miR-196b and miR-1290, that were relatively upregulated in latently infected cells. These two miRNAs were also shown to directly target the 3′UTR of HIV-1 transcripts, while overexpression and knockdown experiments conducted using lab cell lines and CD4 + T-cells from HIV-1-infected patients receiving cART revealed the potential of these miRNAs to modulate HIV-1 replication, as evidenced by changes in virus production and infectivity.…”

Section: Cellular Mirnas As Anti-viral Factors In Hiv-1 Replicatiomentioning

confidence: 99%

Are microRNAs Important Players in HIV-1 Infection? An Update

Muthukumar

Pandhare

Dash

2018

Viruses

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HIV-1 has already claimed over 35 million human lives globally. No curative treatments are currently available, and the only treatment option for over 36 million people currently living with HIV/AIDS are antiretroviral drugs that disrupt the function of virus-encoded proteins. However, such virus-targeted therapeutic strategies are constrained by the ability of the virus to develop drug-resistance. Despite major advances in HIV/AIDS research over the years, substantial knowledge gaps exist in many aspects of HIV-1 replication, especially its interaction with the host. Hence, understanding the mechanistic details of virus–host interactions may lead to novel therapeutic strategies for the prevention and/or management of HIV/AIDS. Notably, unprecedented progress in deciphering host gene silencing processes mediated by several classes of cellular small non-coding RNAs (sncRNA) presents a promising and timely opportunity for developing non-traditional antiviral therapeutic strategies. Cellular microRNAs (miRNA) belong to one such important class of sncRNAs that regulate protein synthesis. Evidence is mounting that cellular miRNAs play important roles in viral replication, either usurped by the virus to promote its replication or employed by the host to control viral infection by directly targeting the viral genome or by targeting cellular proteins required for productive virus replication. In this review, we summarize the findings to date on the role of miRNAs in HIV-1 biology.

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“…C11 cells are a type of HIV-1 latently infected cells constructed by our lab. 8 , 27 , 28 , 29 , 30 , 31 , 32 YA were derived from Jurkat T cells infected with HIV-1 pseudovirus carrying the eGFP reporter gene. 8 , 27 Both of them were cultured in RPMI 1640 medium with 10% FBS (Gibco, Grand Island, NY, USA), 100 U/mL penicillin, and 100 μg/mL streptomycin (Invitrogen, Shanghai, China) at 37°C under 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Zinc-Finger Nucleases Induced by HIV-1 Tat Excise HIV-1 from the Host Genome in Infected and Latently Infected Cells

Liu

et al. 2018

Molecular Therapy - Nucleic Acids

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Highly active anti-retroviral therapy (HAART) cannot clear infected cells harboring HIV-1 proviral DNA from HIV-1-infected patients. We previously demonstrated that zinc-finger nucleases (ZFNs) can specifically and efficiently excise HIV-1 proviral DNA from latently infected human T cells by targeting long terminal repeats (LTRs), a novel and alternative antiretroviral strategy for eradicating HIV-1 infection. To prevent unwanted off-target effects from constantly expressed ZFNs, in this study, we engineered the expression of ZFNs under the control of HIV-1 LTR, by which ZFN expression can be activated by the HIV-1 (Trans-Activator of Transcription) Tat protein. Our results show that functional expression of ZFNs induced by Tat excise the integrated proviral DNA of HIV-NL4-3-eGFP in approximately 30% of the population of HIV-1-infected cells. The results from HIV-1-infected human primary T cells and latently infected T cells treated with the inducible ZFNs further validated that proviral DNA can be excised. Taken together, positively regulated expression of ZFNs in the presence of HIV-1 Tat may provide a safer and novel implementation of genome-editing technology for eradicating HIV-1 proviral DNA from infected host cells.

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Two cellular microRNAs, miR-196b and miR-1290, contribute to HIV-1 latency

Cited by 39 publications

References 63 publications

Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1

Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1

Are microRNAs Important Players in HIV-1 Infection? An Update

Zinc-Finger Nucleases Induced by HIV-1 Tat Excise HIV-1 from the Host Genome in Infected and Latently Infected Cells

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