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Inhibition of Poly(ADP-ribose)polymerase impairs Epstein Barr Virus lytic cycle progression

Stefania Mattiussi1 email, Italo Tempera1 email, Giulia Matusali2 email, Giulia Mearini2 email, Luisa Lenti3 email, Silvia Fratarcangeli1 email, Luciana Mosca1 email, Maria D'Erme1 email and Elena Mattia2 email

Dept. of Biochemical Sciences, University "Sapienza", P.le Aldo Moro, 5, 00185, Rome, Italy

Dept. of Public Health Sciences, University "Sapienza", P.le Aldo Moro, 5, 00185, Rome, Italy

Dept. of Experimental Medicine, University "Sapienza", V.le Regina Elena 324, 00161 Rome, Italy

author email corresponding author email

Infectious Agents and Cancer 2007, 2:18doi:10.1186/1750-9378-2-18

Published: 11 October 2007

Abstract

Background

Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins involved in several cellular events as well as in processes that characterize the infective cycle of some viruses. In the present study, we investigated the role of poly(ADP-ribosylation) on Epstein-Barr Virus (EBV) lytic cycle activation.

Results

Inhibition of PARP-1 by 3-aminobenzamide (3-ABA) during EBV induction, diminished cell damage and apoptosis in the non-productive Raji cell line while markedly reducing the release of viral particles in the productive Jijoye cells. Furthermore, incubation with 3-ABA up-regulated the levels of LMP1 and EBNA2 latent viral proteins. At the same time, it slightly affected the expression of the immediate early BZLF1 gene, but largely down-regulated the levels of the early BFRF1 protein. The modulation of the expression of both latent and lytic EBV genes appeared to be post-transcriptionally regulated.

Conclusion

Taken together the data indicate that PARP-1 plays a role in the progression of EBV lytic cycle and therefore, PARP inhibitors might represent suitable pharmacological adjuncts to control viral spread in EBV productive infection.


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