Last update 01 Nov 2024

HIV-1 Vpr

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with HIV-1 Vpr

HIV-1 Vpr inhibitors(Fudan University)

Target

HIV-1 Vpr

Mechanism

HIV-1 Vpr inhibitors

Active Org.

Fudan University

Originator Org.

Fudan University

Active Indication

HIV Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

VTD227

Target

HIV-1 Vpr

Mechanism

HIV-1 Vpr inhibitors

Active Org.

Riken Corp.

Originator Org.

Riken Corp.

Active Indication

HIV Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HIV-1 Vpr

100 Translational Medicine associated with HIV-1 Vpr

0 Patents (Medical) associated with HIV-1 Vpr

Literatures (Medical) associated with HIV-1 Vpr

01 Jul 2024·The American Journal of Pathology

Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice

Article

Author: Kopp, Jeffrey B ; Knepper, Mark A ; He, John Cijiang ; Lee, Hewang ; Winkler, Cheryl A ; Zhao, Yongmei ; Jose, Pedro A ; Hewitt, Stephen ; Heymann, Jurgen ; Chung, Joon-Yong ; Kino, Tomoshige ; Latt, Khun Zaw ; Reece, Jeff M ; Ishimoto, Yu ; Lee, Kyung ; Okamoto, Koji ; Abedini, Amin ; Susztak, Katalin ; Sun, Zeguo ; Dagur, Pradeep ; Rosenberg, Avi Z ; Yoshida, Teruhiko ; Shrivastav, Shashi

Although hyponatremia and salt wasting are common in patients with HIV/AIDS, the understanding of their contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the distal tubules and on the expression level of the Slc12a3 gene, encoding the sodium-chloride cotransporter (which is responsible for sodium reabsorption in distal nephron segments), single-nucleus RNA sequencing was performed on kidney cortices from three wild-type (WT) and three Vpr transgenic (Vpr Tg) mice. The percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05); in Vpr Tg mice, Slc12a3 expression was not significantly different in DCT cells. The Pvalb⁺ DCT1 subcluster had fewer cells in Vpr Tg mice compared with those in WT mice (P < 0.01). Immunohistochemistry revealed fewer Slc12a3⁺Pvalb⁺ DCT1 segments in Vpr Tg mice. Differential gene expression analysis between Vpr Tg and WT samples in the DCT cluster showed down-regulation of the Ier3 gene, which is an inhibitor of apoptosis. The in vitro knockdown of Ier3 by siRNA transfection induced apoptosis in mouse DCT cells. These observations suggest that the salt-wasting effect of Vpr in Vpr Tg mice is likely mediated by Ier3 down-regulation in DCT1 cells and loss of Slc12a3⁺Pvalb⁺ DCT1 segments.

01 May 2023·European Journal of Clinical Investigation

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

Review

Author: Jansen Van Vuren, Esmé ; Asia, Levanco K. ; Williams, Monray E.

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

01 Apr 2023·AIDS Research and Human Retroviruses

HIV-1 Subtype C Vpr Amino Acid Residue 45Y and Specific Conserved Fragments Are Associated with Neurocognitive Impairment and Markers of Viral Load

Article

Author: Seedat, Soraya ; Engelbrecht, Susan ; Nyandoro, George ; Paul, Robert H. ; Glashoff, Richard Helmuth ; Joska, John A. ; Jacobs, Graeme Brendon ; Ruhanya, Vurayai

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

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HIV-1 Vpr

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