scholarly journals HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2158
Author(s):  
Kristen A. McLaurin ◽  
Michael Harris ◽  
Victor Madormo ◽  
Steven B. Harrod ◽  
Charles F. Mactutus ◽  
...  
Keyword(s):  
Viral Protein ◽  
High Performance ◽  
Dopaminergic System ◽  
Critical Evaluation ◽  
Pharmacological Action ◽  
Primary Treatment ◽  
Additional Line ◽  
Fast Scan Cyclic Voltammetry ◽  
Neurocognitive Impairments ◽  
Hiv 1

Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function.

Diversified Synthetic Pathway of 1, 4-Dihydropyridines: A Class of Pharmacologically Important Molecules

2020 ◽  
Vol 20 ◽  
Author(s):  
Shubham Khot ◽  
Pratibha B. Auti ◽  
Samrat A. Khedkar
Keyword(s):  
Pharmacological Action ◽  
Heterocyclic Ring ◽  
Channel Blockers ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Current Review ◽  
Regulator Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Hiv 1 ◽  
Dihydropyridine Derivatives

: The current review discusses the different synthetic pathways for one of the most important and interesting heterocyclic ring systems 1,4-dihydropyridine. This cyclic system depicts diverse pharmacological action at several receptors, channels, and enzymes. Dihydropyridine moiety plays an important role in several calcium-channel blockers. Moreover, it has been exploited for the treatment of a variety of cardiovascular diseases due to its potential antihypertensive, anti-angina, vasodilator, and cardiac depressant activities. Furthermore, it also shows antibacterial, anticancer, antileishmanial, anticoagulant, anticonvulsant, anti-tubercular, antioxidant, antiulcer, and neuroprotective properties. Several reports have demonstrated dihydropyridine derivatives as a potentiator of cystic fibrosis transmembrane conductance regulator protein, potent antimalarial agent and HIV-1 protease inhibitor. Herein, we have briefly reviewed different novel chemistry and synthesis of 1,4-dihydropyridine.

scholarly journals Effects of Gag Mutation and Processing on Retroviral Dimeric RNA Maturation

2006 ◽  
Vol 80 (3) ◽  
pp. 1242-1249 ◽  
Author(s):  
William Fu ◽  
Que Dang ◽  
Kunio Nagashima ◽  
Eric O. Freed ◽  
Vinay K. Pathak ◽  
...  
Keyword(s):  
Viral Protein ◽  
Leukemia Virus ◽  
Viral Rna ◽  
Host Cells ◽  
Protein Cleavage ◽  
Rna Packaging ◽  
Virus Rna ◽  
Rna Dimer ◽  
Rna Maturation ◽  
Hiv 1

ABSTRACT After their release from host cells, most retroviral particles undergo a maturation process, which includes viral protein cleavage, core condensation, and increased stability of the viral RNA dimer. Inactivating the viral protease prevents protein cleavage; the resulting virions lack condensed cores and contain fragile RNA dimers. Therefore, protein cleavage is linked to virion morphological change and increased stability of the RNA dimer. However, it is unclear whether protein cleavage is sufficient for mediating virus RNA maturation. We have observed a novel phenotype in a murine leukemia virus capsid mutant, which has normal virion production, viral protein cleavage, and RNA packaging. However, this mutant also has immature virion morphology and contains a fragile RNA dimer, which is reminiscent of protease-deficient mutants. To our knowledge, this mutant provides the first evidence that Gag cleavage alone is not sufficient to promote RNA dimer maturation. To extend our study further, we examined a well-defined human immunodeficiency virus type 1 (HIV-1) Gag mutant that lacks a functional PTAP motif and produces immature virions without major defects in viral protein cleavage. We found that the viral RNA dimer in the PTAP mutant is more fragile and unstable compared with those from wild-type HIV-1. Based on the results of experiments using two different Gag mutants from two distinct retroviruses, we conclude that Gag cleavage is not sufficient for promoting RNA dimer maturation, and we propose that there is a link between the maturation of virion morphology and the viral RNA dimer.

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

scholarly journals Mutational analysis of HIV-1 viral protein U at Ser52 and Ser56 among the HIV-1 infected patients of Manipur

2016 ◽  
Vol 15 (1) ◽  
pp. 42-46
Author(s):  
Adhikarimayum Lakhikumar Sharma ◽  
Thiyam Ramsing Singh ◽  
Khuraijam Ranjana Devi ◽  
Lisam Shanjukumar Singh
Keyword(s):  
Viral Protein ◽  
Mutational Analysis ◽  
Viral Protein U ◽  
Hiv 1

scholarly journals The Susceptibility of Primate Lentiviruses to Nucleosides and Vpx during Infection of Dendritic Cells Is Regulated by CA

2015 ◽  
Vol 89 (7) ◽  
pp. 4030-4034 ◽  
Author(s):  
Véronique Barateau ◽  
Xuan-Nhi Nguyen ◽  
Fanny Bourguillault ◽  
Grégory Berger ◽  
Stéphanie Cordeil ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Simian Immunodeficiency Virus ◽  
Viral Protein ◽  
Immunodeficiency Virus ◽  
Protein X ◽  
Primate Lentiviruses ◽  
Species Specific ◽  
Hiv 1

The block toward human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) can be relieved by Vpx (viral protein X), which degrades sterile alpha motif-hydroxylase domain 1 (SAMHD1) or by exogenously added deoxynucleosides (dNs), lending support to the hypothesis that SAMHD1 acts by limiting deoxynucleoside triphosphates (dNTPs). This notion has, however, been questioned. We show that while dNs and Vpx increase the infectivity of HIV-1, only the latter restores the infectivity of a simian immunodeficiency virus of macaques variant, SIVMACΔVpx virus. This distinct behavior seems to map to CA, suggesting that species-specific CA interactors modulate infection of DCs.

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 Intracerebroventricular injection of ouabain causes mania-like behavior in mice through D2 receptor activation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexander Lopachev ◽  
Anna Volnova ◽  
Anna Evdokimenko ◽  
Denis Abaimov ◽  
Yulia Timoshina ◽  
...  
Keyword(s):  
Mouse Model ◽  
Histological Analysis ◽  
Dopaminergic System ◽  
D2 Receptor ◽  
Brain Structures ◽  
Receptor Activation ◽  
Intracerebroventricular Injection ◽  
Fast Scan Cyclic Voltammetry ◽  
The Central Nervous System ◽  
Brain Ventricle

Abstract Intracerebroventricular (ICV) administration of ouabain, an inhibitor of the Na, K-ATPase, is an approach used to study the physiological functions of the Na, K-ATPase and cardiotonic steroids in the central nervous system, known to cause mania-like hyperactivity in rats. We describe a mouse model of ouabain-induced mania-like behavior. ICV administration of 0.5 µl of 50 µM (25 pmol, 14.6 ng) ouabain into each lateral brain ventricle results in increased locomotor activity, stereotypical behavior, and decreased anxiety level an hour at minimum. Fast-scan cyclic voltammetry showed that administration of 50 µM ouabain causes a drastic drop in dopamine uptake rate, confirmed by elevated concentrations of dopamine metabolites detected in the striatum 1 h after administration. Ouabain administration also caused activation of Akt, deactivation of GSK3β and activation of ERK1/2 in the striatum of ouabain-treated mice. All of the abovementioned effects are attenuated by haloperidol (70 µg/kg intraperitoneally). Observed effects were not associated with neurotoxicity, since no dystrophic neuron changes in brain structures were demonstrated by histological analysis. This newly developed mouse model of ouabain-induced mania-like behavior could provide a perspective tool for studying the interactions between the Na,K-ATPase and the dopaminergic system.

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