Resveratrol inhibition of herpes simplex virus replication.
Animals; Antiviral Agents/*pharmacology/toxicity; Cell Cycle/drug effects; Cell Line; Cercopithecus aethiops; Herpesvirus 1; Herpesvirus 2; Human/*drug effects/physiology; Humans; Immediate-Early Proteins/antagonists & inhibitors/biosynthesis; Mice; Resveratrol; Stilbenes/*pharmacology/toxicity; Vero Cells; Virus Latency/drug effects/physiology; Virus Replication/*drug effects/physiology
Resveratrol, a phytoalexin, was found to inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) replication in a dose-dependent, reversible manner. The observed reduction in virus yield was not caused by the direct inactivation of HSV by resveratrol nor inhibition of virus attachment to the cell. The chemical did, however, target an early event in the virus replication cycle since it was most effective when added within 1 h of cell infection, less effective if addition was delayed until 6 h post-infection and not effective if added 9 h post-infection. Resveratrol was also found to delay the cell cycle at S-G2-M interphase, inhibit reactivation of virus from latently-infected neurons and reduce the amount of ICP-4, a major immediate early viral regulatory protein, that is produced when compared to controls. These results suggest that a critical early event in the viral replication cycle, that has a compensatory cellular counterpart, is being adversely affected.
Docherty J J; Fu M M; Stiffler B S; Limperos R J; Pokabla C M; DeLucia A L
Antiviral research
1999
1999-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0166-3542(99)00042-x" target="_blank" rel="noreferrer noopener">10.1016/s0166-3542(99)00042-x</a>
Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells.
Animals; Antiviral Agents/*pharmacology; Cell Nucleus/chemistry; Cercopithecus aethiops; Cytoplasm/chemistry; DNA; Electrophoretic Mobility Shift Assay; Fluorescence; Herpesvirus 1; Herpesvirus 2; Human/drug effects/genetics/*growth & development; Human/drug effects/genetics/*physiology; I-kappa B Proteins/metabolism; Messenger/biosynthesis; Microscopy; NF-kappa B/*metabolism; NF-KappaB Inhibitor alpha; Polymerase Chain Reaction; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; RNA; Stilbenes/*pharmacology; Transcription Factor RelA/metabolism; Vero Cells; Viral/biosynthesis; Virus Replication/*drug effects
Resveratrol inhibits herpes simplex virus (HSV) replication by an unknown mechanism. Previously it was suggested that this inhibition may be mediated through a cellular factor essential for HSV replication [Docherty, J.J., Fu, M.M., Stiffler, B.S., Limperos, R.J., Pokabla, C.M., DeLucia, A.L., 1999. Resveratrol inhibition of herpes simplex virus replication. Antivir. Res. 43,
Faith Seth A; Sweet Thomas J; Bailey Erin; Booth Tristan; Docherty John J
Antiviral research
2006
2006-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.antiviral.2006.06.011" target="_blank" rel="noreferrer noopener">10.1016/j.antiviral.2006.06.011</a>
Effect of resveratrol on herpes simplex virus vaginal infection in the mouse.
Animals; Antiviral Agents/administration & dosage/pharmacology/*therapeutic use; Drug Evaluation; Female; Herpes Genitalis/*drug therapy/pathology/virology; Herpesvirus 1; Herpesvirus 2; Human/*drug effects/physiology; Human/drug effects/isolation & purification/physiology; Mice; Placebos; Preclinical; Resveratrol; Stilbenes/administration & dosage/pharmacology/*therapeutic use; Survival Analysis; Vaginal Diseases/*drug therapy/virology; Viral Plaque Assay; Virus Replication/drug effects
Resveratrol (3,5,4'-trihydroxystilbene) is a natural component of certain foods, such as grapes, that, when topically applied, has been shown to limit HSV-1 lesion formation in the skin of mice [Antiviral Res. 61:19-26, 2004]. To determine if it is active on genital HSV infection, the vagina of mice were infected with HSV-2 or HSV-1 and treated with a cream formulation of resveratrol. Mice were evaluated daily for extravaginal disease and vaginal swabs were taken regularly and assayed for infectious virus. Initial studies demonstrated that 19% resveratrol cream administered intravaginally five times a day for 5 days beginning 1h after infection significantly reduced HSV-2 replication beginning on day 1 of infection and prevented extravaginal disease when compared to animals treated with placebo. When resveratrol was tested at a concentration of 6.25% and 12.5% administered five times a day, 6.25% limited virus replication only on day 1 and delayed development of extravaginal disease by 1 day. However, 12.5% resveratrol inhibited HSV-2 replication beginning on day 1 and abolished extravaginal disease. If the number of applications per day was reduced to three for 5 days, 12.5% resveratrol inhibited HSV-2 replication only on day 1, while 19% resveratrol inhibited it throughout the 9-day assay period. When the animals with three treatments per day were examined for extravaginal disease, it was found that 12.5% resveratrol was ineffective when compared to placebo, while animals treated with 19% resveratrol did not exhibit extravaginal disease. When treatment was delayed 6h, 12.5% resveratrol did not inhibit HSV-2 replication or extravaginal lesion formation, but 19% resveratrol did. When resveratrol was used to treat vaginal HSV-1 infection, it was found that 12.5% resveratrol did not limit replication or prevent extravaginal lesion formation. In contrast, 19% resveratrol did significantly limit vaginal HSV-1 replication and reduced extravaginal lesion formation, but the latter was not significant. Mortality rates in placebo-treated animals was 37%, 6.25% resveratrol-treated animals was 40%, 12.5% resveratrol-treated animals was 24%, and 19% resveratrol-treated animals was 3%. Collectively, these results demonstrate that resveratrol cream inhibits or reduces HSV replication in the vagina of mice and limits extravaginal disease.
Docherty John J; Fu Ming Ming; Hah Jennifer M; Sweet Thomas J; Faith Seth A; Booth Tristan
Antiviral research
2005
2005-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.antiviral.2005.06.008" target="_blank" rel="noreferrer noopener">10.1016/j.antiviral.2005.06.008</a>
HSV-2 ICP34.5 protein modulates herpes simplex virus glycoprotein processing.
*Protein Processing; Animals; Cercopithecus aethiops; Cloning; Gene Expression; Herpesvirus 1; Herpesvirus 2; Human/*genetics; Molecular; Post-Translational; Vero Cells; Viral Envelope Proteins/*metabolism; Viral Proteins/genetics/*metabolism
The ICP34.5 gene from HSV-2 strain 333 was cloned and, when expressed in Vero cells, enhanced the efficiency and extent of glycoprotein processing of glycoprotein C (gC1), a representative viral glycoprotein, during infection with
Chatterjee Somik; Wang Jason W; Cismowski Mary J; Bower John R; Rosenthal Kenneth Steven
Archives of virology
2009
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00705-009-0341-9" target="_blank" rel="noreferrer noopener">10.1007/s00705-009-0341-9</a>