Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques DOI Creative Commons
Alexandre Laliberté, Caterina Prelli Bozzo,

Christiane Stahl‐Hennig

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(12), P. 108351 - 108351

Published: Oct. 27, 2023

The accessory viral protein R (Vpr) is encoded by all primate lentiviruses. Vpr counteracts DNA repair pathways, modulates immune sensing, and induces cell-cycle arrest in cell culture. However, its impact vivo controversial. Here, we show that deletion of vpr associated with delayed replication kinetics, rapid innate activation, development maintenance strong B T responses, increased neutralizing activity against SIVmac239 rhesus macaques. All wild-type SIVmac239-infected animals maintained high loads, five six developed fatal immunodeficiency during ∼80 weeks follow-up. Lack was better preservation CD4+ cells, lower an attenuated clinical course infection most animals. Our results contributes to efficient evasion the full pathogenic potential SIVmac vivo. Inhibition may improve humoral control replication.

Language: Английский

HIV-1 Vpr protein upregulates microRNA-210-5p expression to induce G2 arrest by targeting TGIF2 DOI Creative Commons
Jialu Qiao, Qian Peng, Qian Feng

et al.

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(12), P. e0261971 - e0261971

Published: Dec. 29, 2021

MicroRNAs (miRNAs) are important molecules that mediate virus-host interactions, mainly by regulating gene expression via silencing. Here, we demonstrated HIV-1 infection upregulated miR-210-5p in HIV-1-inoculated cell lines and the serum of HIV-1-infected individuals. Luciferase reporter assays western blotting confirmed a target protein miR-210-5p, TGIF2, is regulated infection. Furthermore, Vpr induced expression. The use inhibitor TGIF2 overexpression showed thereby downregulated which might be one mechanisms used to induce G2 arrest. Moreover, identified transcription factor, NF-κB p50, response protein. In conclusion, mechanism whereby upon infection, targets TGIF2. This pathway was initiated activating promoted These alterations orchestrated miRNA provide new evidence on how interacts with its host during increase our understanding regulates cycle.

Language: Английский

Citations

8
HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load DOI
Vurayai Ruhanya, Graeme Brendon Jacobs, Robert Paul

et al.

AIDS Research and Human Retroviruses, Journal Year: 2022, Volume and Issue: 39(4), P. 166 - 175

Published: Nov. 19, 2022

There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated relationship between subtype C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) treatment-naive individuals. used different bioinformatic tools statistical models to correlate vpr function. identified a tyrosine at position 45 (45Y) signature for histidine (45H) non-impaired The presence 45Y was associated 3.66 times higher GDS, 525 plasma load, 15.84 proviral 60% lower absolute CD4-T cell count compared with those without signature. Additionally, we four conserved fragment sequences, PEDQGPQREPYNEWTLE (5-21), LGQYIY (42-47), TYGDTW (49-54), PEDQGPQREPYNEW (5-18), were load load. implication these findings leads HIV infection worsens progression disease general promoting production provirus, replication depletion CD4+ T cells periphery.

Language: Английский

Citations

6
The influence of viral protein R amino acid substitutions on clinical outcomes in people living with HIV: A systematic review DOI Creative Commons

Levanco K. Asia,

Esmé Jansen van Vuren, Monray E. Williams

et al.

European Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 53(5)

Published: Dec. 29, 2022

The HIV viral protein R (Vpr) is a multifunction involved in the pathophysiology of HIV-1. Recent evidence has suggested that Vpr amino acid substitutions influence HIV-1 and clinical outcomes people living with (PLWH). Several studies have linked to PLWH; however, there no clear consensus as which acids or are most important PLWH. We, therefore, conducted systematic review investigating PLWH.PubMed, Scopus Web Science databases were searched according PRISMA guidelines using search protocol designed specifically for this study.A total 22 included data extraction, comprising 14 cross-sectional 8 longitudinal studies. Results indicated associated specific outcomes, including disease progressions, neurological treatment status. Studies consistently showed substitution 63T was slower progression, whereas 77H 85P significant contribution progression.Vpr-specific may be contributors PLWH, future should consider highlighted review.

Language: Английский

Citations

6
HIV-1 Vpr Induces Degradation of Gelsolin, a Myeloid Cell-Specific Host Factor That Reduces Viral Infectivity by Inhibiting the Expression and Packaging of the HIV-1 Env Glycoprotein DOI Creative Commons
Helena Fábryová,

Sandra Kao,

Sayaka Sukegawa

et al.

mBio, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 5, 2023

Gelsolin (GSN) is a structural actin-binding protein that known to affect actin dynamics in the cell. Using mass spectrometry, we identified GSN as novel Vpr-interacting protein. Endogenous was expressed at detectable levels monocyte-derived macrophages (MDM) and THP-1 cells, but it undetectable level other cell lines tested. The HIV-1 infection of MDM associated with reduction steady-state levels, presumably due Vpr-induced degradation GSN. Indeed, coexpression Viral R (Vpr) transiently transfected HEK293T cells resulted Vpr-dependent proteasomal This effect observed for Vprs from multiple virus isolates. overexpression had no on Gag expression or particle release, reduced packaging envelope (Env) glycoprotein viral infectivity. An analysis splicing patterns did not reveal any GSN-dependent differences, suggesting Env regulated posttranscriptional level. treatment lysosomal inhibitors reversed stability, via enhanced degradation. Our data identify macrophage-specific host antiviral factor reduces Env. IMPORTANCE Despite dramatic progress drug therapies, remains an incurable disease affects millions people worldwide. establishes long-lasting reservoirs are resistant currently available treatments allow rebound whenever therapy interrupted. Macrophages long-lived relatively insensitive HIV-1-induced cytopathicity thus could contribute reservoir. Here, factor, gelsolin, high inhibits infectivity by modulating glycoprotein, which critical spread infection. Importantly, Vpr induces gelsolin counteracts its activity. study provides significant insights into virus-host interactions furthers our understanding importance pathogenesis.

Language: Английский

Citations

3
Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques DOI Creative Commons
Alexandre Laliberté, Caterina Prelli Bozzo,

Christiane Stahl‐Hennig

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(12), P. 108351 - 108351

Published: Oct. 27, 2023

The accessory viral protein R (Vpr) is encoded by all primate lentiviruses. Vpr counteracts DNA repair pathways, modulates immune sensing, and induces cell-cycle arrest in cell culture. However, its impact vivo controversial. Here, we show that deletion of vpr associated with delayed replication kinetics, rapid innate activation, development maintenance strong B T responses, increased neutralizing activity against SIVmac239 rhesus macaques. All wild-type SIVmac239-infected animals maintained high loads, five six developed fatal immunodeficiency during ∼80 weeks follow-up. Lack was better preservation CD4+ cells, lower an attenuated clinical course infection most animals. Our results contributes to efficient evasion the full pathogenic potential SIVmac vivo. Inhibition may improve humoral control replication.

Language: Английский

Citations

2