Grape seed extract proanthocyanidins downregulate HIV- 1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells

Nair, Madhavan; Kandaswami, Chithan; Mahajan, Supriya D.; Nair, Harikrishna N; Chawda, Ram; Shanahan, Thomas; Schwartz, Stanley A.

doi:10.4067/s0716-97602002000300016

Cited by 43 publications

(32 citation statements)

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“…NSC 143101, in particular, is structurally similar to proanthocyanidins (oligomeric proanthocyanidins or condensed tannins), a subgroup of the flavonoid class of polyphenols. Relevant to viral entry, proanthocyanidins have been shown to inhibit entry of herpes simplex virus (25,26) and HIV-1 (22,54). Although no published studies have evaluated the antiviral effect of proanthocyanidins on HCV entry, numerous studies have demonstrated that some flavonoids can inhibit HCV replication and HCVpp entry (3,44,68,74).…”

Section: Discussionmentioning

confidence: 99%

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

Sáinz

Petukhov

et al. 2012

Antimicrob Agents Chemother

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With 2 to 3% of the worldwide population chronically infected, hepatitis C virus (HCV) infection continues to be a major health care burden. Unfortunately, current interferon-based treatment options are not effective in all patients and are associated with significant side effects. Consequently, there is an ongoing need to identify and develop new anti-HCV therapies. Toward this goal, we previously developed a cell-based HCV infection assay for antiviral compound screening based on a low-multiplicity-of-infection approach that uniquely allows for the identification of antiviral compounds that target cell culture-derived HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we report the screening of the NCI Diversity Set II library, containing 1,974 synthesized chemical compounds, and the identification of compounds with specific anti-HCV activity. In combination with toxicity counterscreening, we identified 30 hits from the compound library, 13 of which showed reproducible and dose-dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic concentration [CC 50 ]/50% effective concentration [EC 50 ]) of greater than 6. Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as infectious HCVcc-based assembly and secretion analysis, we determined that different compounds within this group of candidate inhibitors target different steps of viral infection. The compounds identified not only will serve as biological probes to study and further dissect the biology of viral infection but also should facilitate the development of new anti-HCV therapeutic treatments. Hepatitis C virus (HCV) is a hepatotropic enveloped positivestrand RNA virus (family Flaviviridae) that infects the parenchymal cells of the liver (i.e., hepatocytes) (69, 70). HCV infection begins with interaction of the viral particle with the target cell via a relatively undefined multistep process of binding between the virion and multiple cell surface receptors, which include the cluster of differentiation 81 (CD81) tetraspanin protein (7,34,56,80,84), the scavenger receptor class B member I (SR-BI) (also known as SCARB1) (7,30,38,63,83), and the tight-junction proteins claudin-1 (CLDN1) (20) and occludin (OCLN) (8,47,57). In addition to these four host factors, we more recently showed that the cellular Niemann-Pick C1-like 1 (NPC1L1) cholesterol uptake receptor also functions as an HCV entry factor via a virion particle cholesterol-associated mechanism (60), and Lupberger et al. have recently shown that the host cellular epidermal growth factor receptor (EGFR) and ephrin receptor A2 (EphA2) function as cofactors during viral cell entry (49).Following entry, the viral genome (ϳ9.6 kb) is translated by an internal ribosome entry site (IRES)-dependent process into a single viral polyprotein that is subsequently co-and posttranslationally cleaved into structural (core, E1, E2, and p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins by host and viral proteases (29,46). The NS prote...

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Section: Discussionmentioning

confidence: 99%

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

Sáinz

Petukhov

et al. 2012

Antimicrob Agents Chemother

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“…Though the antibacterial effects of GSE have been well studied (2,4,19,29,31), there is very little documentation on its antiviral effects. Nair et al (25,26) studied the antiviral effect of GSE on HIV-1 and showed that GSE significantly downregulated the expression of the HIV-1 coreceptors. Matias et al (23) evaluated the effect of extract obtained from winemaking by-products (composed of both grape skin and seeds) on adenovirus type 5 infection and found that the extract at a concentration of 0.8 mg/ml caused a 5-log 10 -50% tissue culture infective dose (TCID 50 )/ml reduction in total infectious adenovirus type 5.…”

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confidence: 99%

“…(2). Besides bacteria, GSE has also been shown to inhibit the replication and expression of human immunodeficiency virus type 1 (HIV-1) (25,26).…”

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confidence: 99%

Grape Seed Extract for Control of Human Enteric Viruses

D’Souza

2011

Appl Environ Microbiol

132

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Grape seed extract (GSE) is reported to have many pharmacological benefits, including antioxidant, antiinflammatory, anticarcinogenic, and antimicrobial properties. However, the effect of this inexpensive rich source of natural phenolic compounds on human enteric viruses has not been well documented. In the present study, the effect of commercial GSE, Gravinol-S, on the infectivity of human enteric virus surrogates (feline calicivirus, FCV-F9; murine norovirus, MNV-1; and bacteriophage MS2) and hepatitis A virus (HAV; strain HM175) was evaluated. GSE at concentrations of 0.5, 1, and 2 mg/ml was individually mixed with equal volumes of each virus at titers of ϳ7 log 10 PFU/ml or ϳ5 log 10 PFU/ml and incubated for 2 h at room temperature or 37°C. The infectivity of the recovered viruses after triplicate treatments was evaluated by standardized plaque assays. At high titers (ϳ7 log 10 PFU/ml), FCV-F9 was significantly reduced by 3.64, 4.10, and 4.61 log 10 PFU/ml; MNV-1 by 0.82, 1.35, and 1.73 log 10 PFU/ml; MS2 by 1.13, 1.43, and 1.60 log 10 PFU/ml; and HAV by 1.81, 2.66, and 3.20 log 10 PFU/ml after treatment at 37°C with 0.25, 0.50, and 1 mg/ml GSE, respectively (P < 0.05) in a dose-dependent manner. GSE treatment of low titers (ϳ5 log 10 PFU/ml) at 37°C also showed viral reductions. Room-temperature treatments with GSE caused significant reduction of the four viruses, with higher reduction for low-titer FCV-F9, MNV-1, and HAV compared to high titers. Our results indicate that GSE shows promise for application in the food industry as an inexpensive novel natural alternative to reduce viral contamination and enhance food safety.Grapes are one of the world's leading fruit crops, with production rates at more than 50 million tons a year (34). Grape seeds, which are by-products of wine and the grape juice industries, are shown to contain large quantities of phenolic compounds such as gallic acid and monomeric flavan-3-ols catechin, epicatechin, gallocatechin, epigallocatechin, and epicatechin-3-O-gallate, as well as dimeric, trimeric, and polymeric proanthocyanidins (PAC) (37). Grape seed extract (GSE) reportedly has many pharmacological and health benefits that include antioxidant, cardioprotective, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, anticarcinogenic, and antiaging effects (28,47,48).Recently, GSE has gained increasing attention in the food industry because of its associated antimicrobial properties. Rhodes et al. (31) showed that GSE at a concentration of 0.25 mg/ml decreased Listeria monocytogenes from 10 6 to 10 7

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“…Further, we have also shown that flavonoids from grape seed extracts downregulates the expression of HIV-1 entry co-receptors, CCR2b, CCR3 and CCR5 in normal PBMCs [26] , which suggests that flavonoids can interfere with the binding of the virus to the cell receptor and, thus can prevent HIV entry into the normal lymphocyte. In addition, the findings from this study support data demonstrating the ability of quercetin to modulate a variety of inflammatory cytokines and their role in HIV infection.…”

Section: Discussionmentioning

confidence: 99%

The Flavonoid, Quercetin, Inhibits HIV-1 Infection in Normal Peripheral Blood Mononuclear Cells

Nair¹

2009

American Journal of Infectious Diseases

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Problem statement: Flavonoids and related polyphenols, have been known to possess cardioprotective, anti-tumor, anti-inflammatory, anti-allergic and anti-viral activities. Previous studies have shown that flavonoid, quercetin significantly downregulates expression of pro-inflammatory cytokines in cultured cells via modulation of NFκB and p38MAPK signaling pathways. In the current study, we hypothesize that quercetin exerts anti-HIV activity by differential modulation of pro-and anti-inflammatory cytokine expression in normal PBMCs. Approach: Cultures of PBMC received either different concentrations of quercetin (1-50 µM) or media alone. The anti-HIV effects of quercetin was evaluated in an in vitro infection model by quantitaing the HIV-1 LTR gene suppression by quantitative Real Time PCR, HIV-1 p24 antigen production by ELISA and viral infectivity by MAGI cell assay. Results: Our results showed that quercetin significantly downregulates p24 antigen production, LTR gene expression and viral infectivity in a dose dependent manner (5-50 µM) as compared to HIV infected untreated control PBMCs. Further, we reported that quercetin significantly downregulated the expression of the pro-inflammatory cytokine, TNF-α with concomitant upregulation of anti-inflammatory cytokine IL-13 as determined by measurement of gene expression and protein production. A higher level of IL-13 is known to inhibit TNF-α production and also HIV-1 infection. Thus, differential modulation of pro-and anti-inflammatory cytokines could be one of the possible mechanisms for the anti-HIV effects of quercetin. Conclusion: Better understanding of the mechanisms underlying the anti-HIV effects of quercetin may help to develop a new neutraceutical agent useful in the treatment of HIV-1 infected subjects in conjunction with conventional therapeutic regimens.

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Grape seed extract proanthocyanidins downregulate HIV- 1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells

Cited by 43 publications

References 0 publications

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

Grape Seed Extract for Control of Human Enteric Viruses

The Flavonoid, Quercetin, Inhibits HIV-1 Infection in Normal Peripheral Blood Mononuclear Cells

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