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

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

doi:10.2174/1570162x17666190218145048

Cited by 8 publications

(5 citation statements)

References 69 publications

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“…We primarily investigated the influence of BMAL1, REV-ERB, and ROR on HIV-1 replication; however, other circadian factors could also play a role as a Per1 short isoform was shown to inhibit HIV-1 transcription in resting CD4 T cells. 57 …”

Section: Discussionmentioning

confidence: 99%

Molecular components of the circadian clock regulate HIV-1 replication

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Molecular components of the circadian clock regulate HIV-1 replication

et al. 2023

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“…For instance, one of the HIV-1 entry receptors C-X-C chemokine receptor 4 (CXCR4) showed diurnal variation 56 which could result in time-of-day dependent viral entry. We primarily investigated the influence of BMAL1, REV-ERB and ROR on HIV-1 replication, however, other circadian factors could also play a role as a Per1 short isoform was shown to inhibit HIV-1 transcription in resting CD4 T cells 57 .…”

Section: Discussionmentioning

confidence: 99%

Circadian regulation of human immunodeficiency virus type 1 replication

Borrmann

Ulkar

Kliszczak

et al. 2022

Preprint

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Human immunodeficiency virus 1 (HIV-1) is a life-threatening pathogen that still lacks curative therapies or vaccines. Circadian rhythms are endogenous daily oscillations that coordinate an organism’s response to its environment and invading pathogens. Recent reports of diurnal variation in peripheral viral load in HIV-1 infected subjects highlights the need for mechanistic studies. Here, we demonstrate rhythmic HIV-1 replication in circadian-synchronised model systems and show the circadian transcription factors, BMAL1 and REV-ERB, bind conserved motifs in the HIV-1 promoter. REV-ERB competes with ROR for binding to the same regulatory motif, and we uncover a role for ROR inhibitors to perturb rhythmic HIV-1 replication and host gene expression. We demonstrate that many HIV-1 host factors are circadian regulated and likely to define rhythmic viral replication. In summary, this study increases our understanding of the mechanisms underlying the circadian regulation of HIV that can inform HIV therapy and management.

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“…It is reported that the nuclear receptor may be involved in induction of amino acid and lipid metabolism, potentially required for recovery from influenza virus infection (39). Per-1, encoded by PER1, is a novel negative regulator of HIV-1 transcription (40). It is suggested that upregulated expression of PER1 regulated influenza virus infection through the same mechanism.…”

Section: Discussionmentioning

confidence: 99%

Development of Novel Anti-influenza Thiazolides with Relatively Broad-Spectrum Antiviral Potentials

Zhao¹,

Yan²,

Dai³

et al. 2020

Antimicrob Agents Chemother

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Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug resistance to specific anti-influenza virus drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug, nitazoxanide, with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza virus potentials, with 10-fold improvement compared to results with nitazoxanide, and were effective against a variety of influenza virus subtypes including oseltamivir-resistant strains. Notably, the combination using compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effects against oseltamivir-resistant strains. Mode-of-action analysis demonstrated that compounds 4a/4d acted at the late phase of the viral infection cycle through inhibiting viral RNA transcription and replication. Further experiments showed that treatment with compounds 4a/4d significantly inhibited influenza virus infection in human lung organoids, suggesting the druggability of the novel thiazolides. In-depth transcriptome analysis revealed a series of upregulated cellular genes that may contribute to the antiviral activities of 4a/4d. Together, the results of our study indicated the direction to optimize nitazoxanide as an anti-influenza drug and discovered two candidates with novel structures, compounds 4a/4d, that have relatively broad-spectrum antiviral potentials.

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

Cited by 8 publications

References 69 publications

Molecular components of the circadian clock regulate HIV-1 replication

Molecular components of the circadian clock regulate HIV-1 replication

Circadian regulation of human immunodeficiency virus type 1 replication

Development of Novel Anti-influenza Thiazolides with Relatively Broad-Spectrum Antiviral Potentials

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