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

Mattiussi S, Tempera I, Matusali G, Mearini G, Lenti L, Fratarcangeli S, Mosca L, D'Erme M, Mattia E - Infect. Agents Cancer (2007)

Bottom Line: 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.The modulation of the expression of both latent and lytic EBV genes appeared to be post-transcriptionally regulated.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemical Sciences, University "Sapienza", P,le Aldo Moro, 5, 00185, Rome, Italy. s.mattiussi@idi.it

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.

No MeSH data available.


Related in: MedlinePlus

Representative microphotographs showing early antigen expression in Raji cells induced with or without 3-ABA. EBV lytic cycle was induced as described in the Methods in the absence (b), or in the presence (c) of 3 mM 3-ABA. Latently infected Raji cells exposed or not to 3-ABA (a) were used as control. At the indicated times (24, 48 and 72 hours) cells were collected and stained with FITC-labeled EA antibodies and Blue Evans dye.
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Figure 1: Representative microphotographs showing early antigen expression in Raji cells induced with or without 3-ABA. EBV lytic cycle was induced as described in the Methods in the absence (b), or in the presence (c) of 3 mM 3-ABA. Latently infected Raji cells exposed or not to 3-ABA (a) were used as control. At the indicated times (24, 48 and 72 hours) cells were collected and stained with FITC-labeled EA antibodies and Blue Evans dye.

Mentions: The effect of PARP inhibition on EBV early antigen expression was therefore evaluated on Raji cells induced in the presence or in the absence of 3-ABA and on latently-infected Raji cells used as controls. Fig. 1 shows representative microphotographs obtained from cells collected at different times during incubation. The image in a) shows control cells, negative for EA staining, independently of the incubation with the PARP-1 inhibitor. The pictures reported in column b) show that after 24 hours incubation with lytic cycle inducers, FITC-labeled antibodies detected EA in a large percentage of the cell population, and the intensity of the fluorescence increased at 48 hours. In comparison, the expression of EA in the presence of 3-ABA (panel c) occurred in a lower number of cells at 24 hours while at 48 hours the percentage of positive cells and the intensity of the signal seemed comparable or even higher than what reported in panel b).


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

Mattiussi S, Tempera I, Matusali G, Mearini G, Lenti L, Fratarcangeli S, Mosca L, D'Erme M, Mattia E - Infect. Agents Cancer (2007)

Representative microphotographs showing early antigen expression in Raji cells induced with or without 3-ABA. EBV lytic cycle was induced as described in the Methods in the absence (b), or in the presence (c) of 3 mM 3-ABA. Latently infected Raji cells exposed or not to 3-ABA (a) were used as control. At the indicated times (24, 48 and 72 hours) cells were collected and stained with FITC-labeled EA antibodies and Blue Evans dye.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2170434&req=5

Figure 1: Representative microphotographs showing early antigen expression in Raji cells induced with or without 3-ABA. EBV lytic cycle was induced as described in the Methods in the absence (b), or in the presence (c) of 3 mM 3-ABA. Latently infected Raji cells exposed or not to 3-ABA (a) were used as control. At the indicated times (24, 48 and 72 hours) cells were collected and stained with FITC-labeled EA antibodies and Blue Evans dye.
Mentions: The effect of PARP inhibition on EBV early antigen expression was therefore evaluated on Raji cells induced in the presence or in the absence of 3-ABA and on latently-infected Raji cells used as controls. Fig. 1 shows representative microphotographs obtained from cells collected at different times during incubation. The image in a) shows control cells, negative for EA staining, independently of the incubation with the PARP-1 inhibitor. The pictures reported in column b) show that after 24 hours incubation with lytic cycle inducers, FITC-labeled antibodies detected EA in a large percentage of the cell population, and the intensity of the fluorescence increased at 48 hours. In comparison, the expression of EA in the presence of 3-ABA (panel c) occurred in a lower number of cells at 24 hours while at 48 hours the percentage of positive cells and the intensity of the signal seemed comparable or even higher than what reported in panel b).

Bottom Line: 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.The modulation of the expression of both latent and lytic EBV genes appeared to be post-transcriptionally regulated.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemical Sciences, University "Sapienza", P,le Aldo Moro, 5, 00185, Rome, Italy. s.mattiussi@idi.it

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.

No MeSH data available.


Related in: MedlinePlus