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

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 EpsteinBarr Virus (EBV) lytic cycle activation.

Biological Effects of MC2050, a Quinazoline‐Based PARP‐1 Inhibitor, in Human Neuroblastoma and EBV‐Positive Burkitt′s Lymphoma Cells

“…In both cell populations, PARP-1 activity was significantly inhibited up to 60 % after 48 h. A longer incu- bation time was performed on Raji cells compared to SH-SY5Y cells because it is well known that the induction of the lytic cycle reaches a maximum after 48 h of treatment. [25] It is well known that reactive oxygen species (ROS) cause DNA damage, which is a main activator of PARP-1. A low basal level of enzyme activity rescues the cells from damage, whereas excessive activation of the enzyme causes cell death.…”

“…Our previous work demonstrated that PARP-1 inhibition by 3-ABA or PJ34 modulates latent and lytic viral gene expression and counteracts EBV lytic cycle progression, www.chemmedchem.org thus exerting a cytoprotective effect. [25] Hence, we evaluated whether MC2050 is able to affect viral protein expression during the lytic cycle. The levels of EBNA1 protein were found to be increased in a time-dependent manner upon induction of EBV in Raji cells treated with MC2050.…”

“…[25][26][27] In order to verify whether MC2050 could modulate EBV gene expression, we evaluated the levels of the viral protein EBNA1, which plays a pivotal role in the replication and partition of plasmid DNA. [28,29] Cell lysates obtained from latently infected and induced Raji cells treated in the presence or absence of the PARP-1 inhibitor, were analyzed by Western blot using antibodies against EBNA1 ( Figure 5).…”

Herpes Simplex Virus 1 Infection Activates Poly(ADP-Ribose) Polymerase and Triggers the Degradation of Poly(ADP-Ribose) Glycohydrolase

“…PARP-1 activity has been implicated in the pathogenesis of several viral infections. It is necessary for efficient integration of the HIV proviral genome (12) as well as lytic infection by Epstein Barr virus (26), but its interactions with alphaherpesviruses are largely unknown.…”

Epstein-Barr Virus Oncoprotein LMP1 Mediates Epigenetic Changes in Host Gene Expression through PARP1

“…Additionally, the PARP1 protein plays an important regulatory role in gene expression, mainly promoting transcriptional activation through epigenetic mechanisms (13,(16)(17)(18). The host also uses PARylation, specifically through the PARP1 protein, to regulate both the lytic and latent infection of EBV (19,20).…”