Resveratrol inhibition of varicella-zoster virus replication in vitro

Docherty, John J.; Sweet, Thomas J.; Bailey, Erin; Faith, Seth A.; Booth, Tristan D.

doi:10.1016/j.antiviral.2006.07.004

Cited by 100 publications

(68 citation statements)

References 27 publications

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“…pSTAT3 in virus-infected cells has been associated with interactions between various host cell kinases and viral factors. A role for cellular kinases in STAT3 activation in VZV-infected cells is suggested by the observation that resveratrol, which inhibits pSTAT3 mediated by cellular kinases, has antiviral activity against VZV (38,39). The role of cellular and viral kinases in pSTAT3 and survivin up-regulation during VZV infection warrants investigation.…”

Section: Discussionmentioning

confidence: 99%

Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis

Sen¹,

Che²,

Rajamani³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Varicella-zoster virus (VZV) is a human α-herpesvirus that causes varicella (chickenpox) during primary infection and zoster (shingles) upon reactivation. Like other viruses, VZV must subvert the intrinsic antiviral defenses of differentiated human cells to produce progeny virions. Accordingly, VZV inhibits the activation of the cellular transcription factors IFN regulatory factor 3 (IRF3) and signal transducers and activators of transcription 1 (STAT1), thereby downregulating antiviral factors, including IFNs. Conversely, in this study, we found that VZV triggers STAT3 phosphorylation in cells infected in vitro and in human skin xenografts in SCID mice in vivo and that STAT3 activation induces the anti-apoptotic protein survivin. Small-molecule inhibitors of STAT3 phosphorylation and survivin restrict VZV replication in vitro, and VZV infection of skin xenografts in vivo is markedly impaired by the administration of the phospho-STAT3 inhibitor S3I-201. STAT3 and survivin are required for malignant transformation caused by γ-herpesviruses, such as Kaposi's sarcoma virus. We show that STAT3 activation is also critical for VZV, a nononcogenic herpesvirus, via a survivin-dependent mechanism. Furthermore, STAT3 activation is critical for the life cycle of the virus because VZV skin infection is necessary for viral transmission and persistence in the human population. Therefore, we conclude that takeover of this major cell-signaling pathway is necessary, independent of cell transformation, for herpesvirus pathogenesis and that STAT3 activation and up-regulation of survivin is a common mechanism important for the pathogenesis of lytic as well as tumorigenic herpesviruses.T he life cycle of varicella-zoster virus (VZV) in the human host depends on its tropism for T cells, skin, and neurons within sensory ganglia (1). As shown in the SCID mouse model of VZV pathogenesis, infected human T cells transport the virus to epidermal cells in human skin xenografts and to neural cells in dorsal root ganglia xenografts (2, 3). VZV establishes latency in sensory ganglia; upon reactivation, the virus migrates to the skin via axonal transport to cause zoster.VZV modulates several signaling pathways to replicate efficiently in vitro, and these regulatory effects are especially important in differentiated skin cells infected in vivo. VZV interferes with IFN induction and signaling via inhibition of IFN regulatory factor 3 (IRF3), NFκB, and STAT1 in vitro and in skin (4, 5). However, the pathogenesis of VZV skin infection requires a mechanism to overcome the constitutive IFNα expression by epidermal cells that accounts for the 10-to 21-d interval between VZV transfer into skin and the appearance of lesions at skin surfaces (6). How VZV overcomes this cutaneous IFN barrier and produces skin vesicles is not known.The STATs are ubiquitous transcription factors with many cellular functions and are at the junction of several cytokinesignaling pathways (7,8). Of the seven STAT family proteins, STAT3 exerts widespread effects through transcri...

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Section: Discussionmentioning

confidence: 99%

Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis

Sen¹,

Che²,

Rajamani³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Since resveratrol has potent antioxidative and anti-inflammatory properties, its antiviral effects have therefore been investigated. Recently, resveratrol was shown to be a potent antiviral molecule against various types of DNA and RNA viruses, including HSV-1 (herpes simplex virus 1), HSV-2, VZV (varicella-zoster virus), HCMV (human cytomegalovirus), and influenza A virus (11)(12)(13)(14)42). Here we demonstrated that resveratrol also possessed anti-RSV properties by using a CYP-induced immunocompromised BALB/c mouse model of RSV infection.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Youn et al demonstrated previously that resveratrol suppressed NF-B activation and COX-2 expression by inhibiting TRIF signaling associated with the Toll-like receptor 3 (TLR3) and TLR4 MyD88-independent pathway by targeting TANK-binding kinase 1 and RIP1 in the TRIF complex (51). In recent years, several studies have demonstrated that resveratrol inhibited viral replication, e.g., influenza A virus, human cytomegalovirus, herpes simplex virus, and varicella-zoster virus, both in vitro and in vivo (11)(12)(13)(14)42).…”

mentioning

confidence: 99%

Resveratrol-Mediated Gamma Interferon Reduction Prevents Airway Inflammation and Airway Hyperresponsiveness in Respiratory Syncytial Virus-Infected Immunocompromised Mice

Zang

Xie

Deng

et al. 2011

J Virol

121

111

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“…It has been shown that RV is effective against a wide variety of viruses (6). RV is reported to strongly inhibit the in vitro and in vivo replication of influenza virus (30) and also has strong antiviral activity against herpes simplex virus type 1 (11)(12)(13)(14), polyomavirus (3), and varicellazoster virus (15).…”

mentioning

confidence: 99%

Grape Seed Extract for Control of Human Enteric Viruses

D’Souza

2011

Appl Environ Microbiol

131

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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

show abstract

Resveratrol inhibition of varicella-zoster virus replication in vitro

Cited by 100 publications

References 27 publications

Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis

Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis

Resveratrol-Mediated Gamma Interferon Reduction Prevents Airway Inflammation and Airway Hyperresponsiveness in Respiratory Syncytial Virus-Infected Immunocompromised Mice

Grape Seed Extract for Control of Human Enteric Viruses

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