MiRNA-103 downmodulates CCR5 expression reducing human immunodeficiency virus type-1 entry and impacting latency establishment in CD4+ T cells DOI Creative Commons

Nicolas Bellini,

Robert Lodge, Tram N. Q. Pham

et al.

iScience, Journal Year: 2022, Volume and Issue: 25(10), P. 105234 - 105234

Published: Sept. 28, 2022

Activated-to-memory transitioning CD4+ T cells display elevated expression of the HIV-1 co-receptor CCR5 and are more prone to latent infection. Here, we show that p53-regulated miRNA-103 downmodulates levels in lymphocytes. We reveal mimics, as well Nutlin-3, an inhibitor Mdm2-mediated p53 degradation, decrease CCR5-dependent Using a dual-reporter virus, subsequently validate cells, Nutlin-3 treatment decreases frequency both productively latently infected via upregulation miRNA-103. Importantly, provide evidence from elite controllers express less than those antiretroviral therapy-naïve progressors, effect linked significant increase levels. By contributing control is likely play key role countering establishment reservoirs vivo.

Language: Английский

Intertwined: SAMHD1 cellular functions, restriction, and viral evasion strategies DOI

Catharina Majer,

Moritz Schüssler, Renate König

et al.

Medical Microbiology and Immunology, Journal Year: 2019, Volume and Issue: 208(3-4), P. 513 - 529

Published: March 16, 2019

Language: Английский

Citations

21
SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity DOI Creative Commons
Simone De Meo, Valentina Dell’Oste, Rosa Molfetta

et al.

PLoS Pathogens, Journal Year: 2020, Volume and Issue: 16(9), P. e1008855 - e1008855

Published: Sept. 28, 2020

SAMHD1 is a host restriction factor that functions to restrict both retroviruses and DNA viruses, based on its nuclear deoxynucleotide triphosphate (dNTP) hydrolase activity limits availability of intracellular dNTP pools. In the present study, we demonstrate expression was increased following human cytomegalovirus (HCMV) infection, with only modest effect infectious virus production. rapidly phosphorylated at residue T592 after infection by cellular cyclin-dependent kinases, especially Cdk2, viral kinase pUL97, resulting in significant fraction phosho-SAMHD1 being relocalized cytoplasm infected fibroblasts, association particles dense bodies. Thus, our findings indicate HCMV-dependent cytoplasmic delocalization inactivation may represent potential novel mechanism HCMV evasion from antiviral activities.

Language: Английский

Citations

19
Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels DOI Creative Commons
Moritz Schüssler, Kerstin Schott, Nina V. Fuchs

et al.

mBio, Journal Year: 2023, Volume and Issue: 14(5)

Published: Oct. 6, 2023

We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of sterile α motif and HD domain-containing protein 1 (SAMHD1) T592 phosphorylation on anti-viral restriction control cellular dNTP levels endogenous, physiologically relevant context. A proper understanding mechanism function SAMHD1 will provide attractive strategies aiming at selectively manipulating without affecting other functions. Even more, our toolkit may inspire further genetic analysis investigation factors inhibiting retroviruses their regulation, leading a deeper intrinsic immunity.

Language: Английский

Citations

6
Downregulation of miRNA-26a by HIV-1 Enhances CD59 Expression and Packaging Impacting Virus Susceptibility to Antibody-Dependent Complement-Mediated Lysis DOI Open Access

Nicolas Bellini,

Chengyu Ye, Oluwaseun Ajibola

et al.

Published: June 5, 2024

MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNAseq profilings miRNAs and mRNAs expressed CD4+ T-lymphocytes upon Our results reveal significant alterations expression profiles infected relative to uninfected cells. One markedly downregulated cells is miRNA-26a. Among putative targets miRNA-26a are CD59 receptor transcripts, which significantly upregulated T-cells. Addition mimics T-cells reduces at both mRNA surface protein levels, validating as a target. Consistent with reported inhibitory role complement-mediated lysis (CML), knocking-out renders progeny virions more prone antibody-dependent CML (ADCML). leads enhanced sensitivity ADCML, condition linked reduction packaging into released virions. Lastly, HIV-1-mediated downregulation shown be dependent on integrated but does not involve viral accessory proteins. Overall, these highlight novel mechanism by limits ADCML upregulating via downmodulation.

Language: Английский

Citations

2
MiRNA-103 downmodulates CCR5 expression reducing human immunodeficiency virus type-1 entry and impacting latency establishment in CD4+ T cells DOI Creative Commons

Nicolas Bellini,

Robert Lodge, Tram N. Q. Pham

et al.

iScience, Journal Year: 2022, Volume and Issue: 25(10), P. 105234 - 105234

Published: Sept. 28, 2022

Activated-to-memory transitioning CD4+ T cells display elevated expression of the HIV-1 co-receptor CCR5 and are more prone to latent infection. Here, we show that p53-regulated miRNA-103 downmodulates levels in lymphocytes. We reveal mimics, as well Nutlin-3, an inhibitor Mdm2-mediated p53 degradation, decrease CCR5-dependent Using a dual-reporter virus, subsequently validate cells, Nutlin-3 treatment decreases frequency both productively latently infected via upregulation miRNA-103. Importantly, provide evidence from elite controllers express less than those antiretroviral therapy-naïve progressors, effect linked significant increase levels. By contributing control is likely play key role countering establishment reservoirs vivo.

Language: Английский

Citations

10