Investigation of HIV‐1 Viral protein R inhibitory activities of twelve Thai medicinal plants and their commercially available major constituents

2021 ◽  
Author(s):  
Amit Jaisi ◽  
Prema Prema ◽  
Siribhorn Madla ◽  
Yuan-E Lee ◽  
Abdi Wira Septama ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Viral Protein ◽  
Viral Protein R ◽  
Thai Medicinal Plants ◽  
Inhibitory Activities ◽  
Hiv 1

scholarly journals Modulation of NKG2D-Mediated Cytotoxic Functions of Natural Killer Cells by Viral Protein R from HIV-1 Primary Isolates

2012 ◽  
Vol 86 (3) ◽  
pp. 1902-1902
Author(s):  
T. N. Q. Pham ◽  
J. Richard ◽  
F. C. A. Gerard ◽  
C. Power ◽  
E. A. Cohen
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Viral Protein ◽  
Killer Cells ◽  
Viral Protein R ◽  
Hiv 1

Virtual Screening for Anti-HIV-1 RT and Anti-HIV-1 PR Inhibitors from the Thai Medicinal Plants Database: A Combined Docking with Neural Networks Approach

2005 ◽  
Vol 8 (5) ◽  
pp. 417-429 ◽  
Author(s):  
Chak Sangma ◽  
Daungmanee Chuakheaw ◽  
Nipa Jongkon ◽  
Kittipong Saenbandit ◽  
Peerapol Nunrium ◽  
...  
Keyword(s):  
Neural Networks ◽  
Virtual Screening ◽  
Medicinal Plants ◽  
Thai Medicinal Plants ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals HIV-1 Integrase-Targeted Short Peptides Derived from a Viral Protein R Sequence

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1858 ◽  
Author(s):  
Xue Zhao ◽  
Mathieu Métifiot ◽  
Evgeny Kiselev ◽  
Jacques Kessl ◽  
Kasthuraiah Maddali ◽  
...  
Keyword(s):  
Viral Protein ◽  
Divalent Metal ◽  
Common Mechanism ◽  
Strand Transfer ◽  
Divalent Metal Ions ◽  
Dna Interactions ◽  
Inhibitory Potency ◽  
New Class ◽  
Viral Protein R ◽  
Hiv 1

HIV-1 integrase (IN) inhibitors represent a new class of highly effective anti-AIDS therapeutics. Current FDA-approved IN strand transfer inhibitors (INSTIs) share a common mechanism of action that involves chelation of catalytic divalent metal ions. However, the emergence of IN mutants having reduced sensitivity to these inhibitors underlies efforts to derive agents that antagonize IN function by alternate mechanisms. Integrase along with the 96-residue multifunctional accessory protein, viral protein R (Vpr), are both components of the HIV-1 pre-integration complex (PIC). Coordinated interactions within the PIC are important for viral replication. Herein, we report a 7-mer peptide based on the shortened Vpr (69–75) sequence containing a biotin group and a photo-reactive benzoylphenylalanyl residue, and which exhibits low micromolar IN inhibitory potency. Photo-crosslinking experiments have indicated that the peptide directly binds IN. The peptide does not interfere with IN-DNA interactions or induce higher-order, aberrant IN multimerization, suggesting a mode of action for the peptide that is distinct from clinically used INSTIs and developmental allosteric IN inhibitors. This compact Vpr-derived peptide may serve as a valuable pharmacological tool to identify a potential new pharmacologic site.

scholarly journals Peptides derived from the C-terminal domain of HIV-1 Viral Protein R in lipid bilayers: Structure, membrane positioning and gene delivery

2020 ◽  
Vol 1862 (2) ◽  
pp. 183149
Author(s):  
Arnaud Marquette ◽  
Christian Leborgne ◽  
Vanessa Schartner ◽  
Evgeniy Salnikov ◽  
Burkhard Bechinger ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Lipid Bilayers ◽  
Viral Protein ◽  
Terminal Domain ◽  
Viral Protein R ◽  
Hiv 1

scholarly journals Viral protein R upregulates expression of ULBP2 on uninfected bystander cells during HIV-1 infection of primary CD4+ T lymphocytes

Virology ◽  
2013 ◽  
Vol 443 (2) ◽  
pp. 248-256 ◽  
Author(s):  
Jonathan Richard ◽  
Tram N.Q. Pham ◽  
Yukihito Ishizaka ◽  
Éric A. Cohen
Keyword(s):  
T Lymphocytes ◽  
Viral Protein ◽  
Viral Protein R ◽  
Bystander Cells ◽  
Hiv 1

scholarly journals The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore

2000 ◽  
Vol 191 (1) ◽  
pp. 33-46 ◽  
Author(s):  
Etienne Jacotot ◽  
Luigi Ravagnan ◽  
Markus Loeffler ◽  
Karine F. Ferri ◽  
Helena L.A. Vieira ◽  
...  
Keyword(s):  
Direct Effect ◽  
Viral Protein ◽  
Mitochondrial Permeability Transition ◽  
Adenine Nucleotide ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Voltage Dependent Anion Channel ◽  
Intact Cells ◽  
Viral Protein R ◽  
Hiv 1

Viral protein R (Vpr) encoded by HIV-1 is a facultative inducer of apoptosis. When added to intact cells or purified mitochondria, micromolar and submicromolar doses of synthetic Vpr cause a rapid dissipation of the mitochondrial transmembrane potential (ΔΨm), as well as the mitochondrial release of apoptogenic proteins such as cytochrome c or apoptosis inducing factor. The same structural motifs relevant for cell killing are responsible for the mitochondriotoxic effects of Vpr. Both mitochondrial and cytotoxic Vpr effects are prevented by Bcl-2, an inhibitor of the permeability transition pore complex (PTPC). Coincubation of purified organelles revealed that nuclear apoptosis is only induced by Vpr when mitochondria are present yet can be abolished by PTPC inhibitors. Vpr favors the permeabilization of artificial membranes containing the purified PTPC or defined PTPC components such as the adenine nucleotide translocator (ANT) combined with Bax. Again, this effect is prevented by addition of recombinant Bcl-2. The Vpr COOH terminus binds purified ANT, as well as a molecular complex containing ANT and the voltage-dependent anion channel (VDAC), another PTPC component. Yeast strains lacking ANT or VDAC are less susceptible to Vpr-induced killing than control cells yet recover Vpr sensitivity when retransfected with yeast ANT or human VDAC. Hence, Vpr induces apoptosis via a direct effect on the mitochondrial PTPC.

scholarly journals SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr)

2016 ◽  
Vol 291 (33) ◽  
pp. 16936-16947 ◽  
Author(s):  
Xiaohong Zhou ◽  
Maria DeLucia ◽  
Jinwoo Ahn
Keyword(s):  
Ubiquitin Ligase ◽  
Viral Protein ◽  
E3 Ubiquitin Ligase ◽  
Down Regulation ◽  
Detailed Mechanism ◽  
Viral Protein R ◽  
Evolutionarily Conserved ◽  
Primate Lentiviruses ◽  
Hiv 1 ◽  
Arrest Activity

Evolutionarily conserved structure-selective endonuclease MUS81 forms a complex with EME1 and further associates with another endonuclease SLX4-SLX1 to form a four-subunit complex of MUS81-EME1-SLX4-SLX1, coordinating distinctive biochemical activities of both endonucleases in DNA repair. Viral protein R (Vpr), a highly conserved accessory protein in primate lentiviruses, was previously reported to bind SLX4 to mediate down-regulation of MUS81. However, the detailed mechanism underlying MUS81 down-regulation is unclear. Here, we report that HIV-1 Vpr down-regulates both MUS81 and its cofactor EME1 by hijacking the host CRL4-DCAF1 E3 ubiquitin ligase. Multiple Vpr variants, from HIV-1 and SIV, down-regulate both MUS81 and EME1. Furthermore, a C-terminally truncated Vpr mutant and point mutants R80A and Q65R, all of which lack G2 arrest activity, are able to down-regulate MUS81-EME1, suggesting that Vpr-induced G2 arrest is not correlated with MUS81-EME1 down-regulation. We also show that neither the interaction of MUS81-EME1 with Vpr nor their down-regulation is dependent on SLX4-SLX1. Together, these data provide new insight on a conserved function of Vpr in a host endonuclease down-regulation.

Anti-HIV-1 protease- and HIV-1 integrase activities of Thai medicinal plants known as Hua-Khao-Yen

2006 ◽  
Vol 105 (1-2) ◽  
pp. 312-315 ◽  
Author(s):  
Supinya Tewtrakul ◽  
Arunporn Itharat ◽  
Pranee Rattanasuwan
Keyword(s):  
Medicinal Plants ◽  
Thai Medicinal Plants ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals HIV-1 Viral Protein R Couples Metabolic inflexibility with White Adipose Tissue Thermogenesis

2021 ◽  
Author(s):  
Neeti Agarwal ◽  
Dinakar Iyer ◽  
Pradip Saha ◽  
Aaron R. Cox ◽  
Yan Xia ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Mouse Models ◽  
White Adipose Tissue ◽  
Viral Protein ◽  
Adipose Tissues ◽  
Adaptive Thermogenesis ◽  
Viral Protein R ◽  
Metabolic Inflexibility ◽  
Hiv 1

Persons living with HIV (PLWH) manifest chronic disorders of brown and white adipose tissues that lead to diabetes and metabolic syndrome. The mechanisms that link viral factors to defective adipose tissue function and abnormal energy balance in PLWH remain incompletely understood. Here, we explored how the HIV accessory protein viral protein R (Vpr) contributes to adaptive thermogenesis in two mouse models and human adipose tissues. Uncoupling protein 1 (UCP1) gene expression was strongly increased in subcutaneous white adipose tissue (WAT) biopsies from PLWH and in subcutaneous WAT of the Vpr mice, with near-equivalent mRNA copy number. Histology and functional studies confirmed beige transformation in subcutaneous but not visceral WAT in the Vpr mice. Measurements of energy balance indicated Vpr mice displayed metabolic inflexibility and could not shift efficiently from carbohydrate to fat metabolism during day-night cycles. Furthermore, Vpr mice showed a marked inability to defend body temperature when exposed to 4<sup>o</sup>C. Importantly, Vpr couples higher tissue catecholamine levels with UCP1 expression independent of β-adrenergic receptors. Our data reveal surprising deficits of adaptive thermogenesis that drive metabolic inefficiency in HIV-1 Vpr mouse models, providing an expanded role for viral factors in the pathogenesis of metabolic disorders in PLWH.

Sign in / Sign up

Export Citation Format

Share Document