Resveratrol Inhibits Human Cytomegalovirus Replication and Virus-Induced Cellular Signaling

Scientists have discovered that 3,4',5-Trihydroxy-trans-stilbene, also known as resveratrol, inhibits human cytomegalovirus replication and virus-induced cellular signaling. This polyphenolic natural product, found in red wine and peanuts, has been shown to have inhibitory activity against inflammation, heart disease, and cancer. The study, conducted by D.L. Evers and colleagues at the University of North Carolina, found that resveratrol blocked the activation of the epidermal growth factor receptor and phosphatidylinositol-3-kinase signal transduction, as well as NF-kappaB and Sp1 transcription factor activation shortly following infection.

Key Takeaways:

• Resveratrol inhibits human cytomegalovirus replication and virus-induced cellular signaling with an IC50 of 1-2 mcM.
• At least 50-fold higher concentrations of resveratrol are required to produce cytotoxicity against growing or stationary human embryonic lung fibroblasts.
• Mechanism of action studies determined that resveratrol blocked virus-induced activation of the epidermal growth factor receptor (EGFR) and phosphatidylinositol-3-kinase signal transduction as well as NF-kappaB and Sp1 transcription factor activation shortly following infection.
• Resveratrol prevented the appearance of immediate-early, early, and late viral proteins and reduced human cytomegalovirus DNA replication to undetectable levels.
• The study found that resveratrol lost substantial antiviral activity when its addition was delayed until 4 hours postinfection.
• The researchers hypothesized that the primary molecular target for resveratrol may be the blockage of epidermal growth factor receptor activation and its downstream effectors.
• Resveratrol was shown to operate during attachment and entry, with compound reversibility and preincubation studies inconsistent with a virucidal mechanism of action.

Statistics:

• IC50 of resveratrol: 1-2 mcM
• Concentration required for cytotoxicity: at least 50-fold higher than the IC50
• Delay before loss of antiviral activity: 4 hours postinfection
• Level of DNA replication reduction: to undetectable levels
• Substance exposed: human cytomegalovirus (HCMV)

Sources:

• Evers, D.L., et al. (2004). 3,4',5-trihydroxy-trans-stilbene (Resveratrol) inhibits human cytomegalovirus replication and virus-induced cellular signaling. Antivir Res, 63(2), 85-95.
• Elsevier Science BV. (Publisher).