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E. Mattia - Effects of resveratrol on Epstein-Barr Virus latent and lytic phases of infection
P(BU)2 or anti Ig. Following EBV activation, two
major viral genes are expressed: BZLF1 and BRLF1.
BZLF1 product is a transcriprion factor and together
with BRLF1 product starts the lytic cascade that
leads to viral DNA replication and production of
viral particles.
We examined the effects of resveratrol on EBV lytic
infection by exposing to the polyphenol cells treated
with EBV lytic cycle-inducing compounds. We found
that EBV activation was largely prevented by resveratrol
as judged by immunofluorescence detection
of EBV early antigens expression. This result was
confirmed by the drastic reduction of the immediate
early antigen BZLF1 expression detected by western
blot analysis; moreover, the increment of the latent
protein LMP1, usually over-expressed during the
early phases of EBV lytic cycle activation, was significantly
reduced (Fig.1). In several types of cancer
cells, treatment with resveratrol resulted in cell cycle
arrest, induction of p53 tumor suppressor protein
and apoptosis. Similarly, resveratrol up-regulated the
tumor suppressor p53 protein both in latently-infected
cells, as well as in cells treated with EBV lytic cycle
activators. Cumulatively, these data indicate that
resveratrol (i) arrests cell cycle and induces apoptosis
of EBV-infected cells (ii) impairs expression of latent
EBV genes (iii) suppresses EBV lytic cycle activation.
Based on these results, experiments are currently carried
out to gain insights into the molecular mechanisms
by which resveratrol affects EBV expression in the two
phases of infection and to identify the viral and cellular
factors involved in cell cycle arrest and apoptosis.
Selected publications
Fig.1 - Effects of resveratrol on EBV lytic cycle activation.
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Galletti R, Masciarelli S, Conti C, Matusali G, Di
Renzo L, Meschini S, Arancia G, Mancini C, Mattia E.
Inhibition of Epstein Barr Virus LMP1 gene expression
in B lymphocytes by antisense oligonucleotides:
uptake and efficacy of lipid-based and receptor-mediated
delivery systems. Antiviral Research 2007, 74:102-10.
Matusali G, De Leo A, Gavioli R, Bertelli L, Di
Renzo L, Mattia E. Down-regulation of proteolytic
complexes following EBV activation in BL cells.
Biochem Biophys Res Commun. 2007, 352:947-52.
Mattiussi S, Tempera I, Matusali G, Mearini G,
Lenti L, Fratarcangeli S, Mosca L, D’Erme M,
Mattia E. Inhibition of Poly(ADP ribose)polymerase
impairs Epstein Barr Virus lytic cycle progression.
Infect Agents Cancer 2007, 2:18.