Limits...
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

Cytofluorymetric analysis of apoptotic Raji cells. Raji cells were induced in the absence or in the presence of 3-ABA as for Fig.1. At the indicated times, cells were collected and subjected to Annexin V-FITC/PI staining as reported in the Methods. The upper part of the figure shows the dot blots of PI vs. Annexin V stain. All parameters and region settings were kept identical throughout all measurements. The table illustrates the percentages of necrotic cells (PI); secondary necrotic cells (PI/A); viable cells (V); Annexin V-positive (apoptotic) cells (A).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2170434&req=5

Figure 2: Cytofluorymetric analysis of apoptotic Raji cells. Raji cells were induced in the absence or in the presence of 3-ABA as for Fig.1. At the indicated times, cells were collected and subjected to Annexin V-FITC/PI staining as reported in the Methods. The upper part of the figure shows the dot blots of PI vs. Annexin V stain. All parameters and region settings were kept identical throughout all measurements. The table illustrates the percentages of necrotic cells (PI); secondary necrotic cells (PI/A); viable cells (V); Annexin V-positive (apoptotic) cells (A).

Mentions: To further investigate the protective effect of 3-ABA during EBV lytic cycle activation the rate of apoptosis was tested by Annexin V assay. Fig. 2 shows the PI versus Annexin V dot plot of a representative experiment performed on Raji cells treated as above described. The data of the cytofluorymetric analysis indicate that after 48 and 72 hours of exposure to the lytic cycle inducing compounds, cell viability was reduced to about 87 and 74%, respectively, while the corresponding measurements of the cells exposed to 3-ABA were 97 and 89%. At the same time points, the percentages of Annexin V-positive cells were 11 and 23%, respectively. However, the fraction of apoptotic cells was markedly lower (1.3 and 7.2%) in the samples incubated in the presence of 3-ABA.


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)

Cytofluorymetric analysis of apoptotic Raji cells. Raji cells were induced in the absence or in the presence of 3-ABA as for Fig.1. At the indicated times, cells were collected and subjected to Annexin V-FITC/PI staining as reported in the Methods. The upper part of the figure shows the dot blots of PI vs. Annexin V stain. All parameters and region settings were kept identical throughout all measurements. The table illustrates the percentages of necrotic cells (PI); secondary necrotic cells (PI/A); viable cells (V); Annexin V-positive (apoptotic) cells (A).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Cytofluorymetric analysis of apoptotic Raji cells. Raji cells were induced in the absence or in the presence of 3-ABA as for Fig.1. At the indicated times, cells were collected and subjected to Annexin V-FITC/PI staining as reported in the Methods. The upper part of the figure shows the dot blots of PI vs. Annexin V stain. All parameters and region settings were kept identical throughout all measurements. The table illustrates the percentages of necrotic cells (PI); secondary necrotic cells (PI/A); viable cells (V); Annexin V-positive (apoptotic) cells (A).
Mentions: To further investigate the protective effect of 3-ABA during EBV lytic cycle activation the rate of apoptosis was tested by Annexin V assay. Fig. 2 shows the PI versus Annexin V dot plot of a representative experiment performed on Raji cells treated as above described. The data of the cytofluorymetric analysis indicate that after 48 and 72 hours of exposure to the lytic cycle inducing compounds, cell viability was reduced to about 87 and 74%, respectively, while the corresponding measurements of the cells exposed to 3-ABA were 97 and 89%. At the same time points, the percentages of Annexin V-positive cells were 11 and 23%, respectively. However, the fraction of apoptotic cells was markedly lower (1.3 and 7.2%) in the samples incubated in the presence of 3-ABA.

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