PARP in the neuropathogenesis of cytomegalovirus infection - Possible role and therapeutic perspective

Abstract

Cytomegalovirus infects the majority of the population globally. Congenital CMV infection acquired through primary maternal infection in pregnancy is the most common intrauterine infection with a high mortality rate due to severe long-term neurodevelopmental sequelae. The demyelination and neuroinflammation during CMV infection have been attributed to altered immune response and ROS-mediated apoptosis. PARP-1 protein is linked to apoptotic neuronal loss with subsequent neurotoxicity and CNS injury as a result of PARP hyperactivation. PARP-1 play a critical role in the establishment of latency including EBV, HHV-8 and HIV. Research on PARP inhibitors recently shows significant progress against neurodegenerative diseases such as Alzheimer's disease and cancer therapy including malignant lymphoma and hepatitis B virus-induced hepatocellular carcinoma. The role of PARP1 in the neuropathogenesis of CMV and the potential of PARP inhibitors in the prevention of neurological sequelae is still elusive. Further studies on the role of PARP on the neuropathogenesis of CMV infection can help thwart neurodegeneration through the potential development of PARP inhibitors such as small molecule inhibitors.