Investigating the p_(53)-dependent Roles of SIRT1 and SIRT2 in Regulating Human Cytomegalovirus Replication

摘要

Sirtuin 1 and Sirtuin 2 (SIRT1 and SIRT2) are NAD~+-dependent deacetylases with multiple important functions, such as regulation of cell survival/apoptosis, cell cycle, and gene expression. Their pathways are frequently hijacked by the virus in order to ensure efficient viral replication. Recent reports have proposed that SIRT1 can play roles during retroviral, papilloma viral, and rhabdoviral infections. However, no such functions have been proposed for SIRT2. Moreover, neither enzyme has been previously demonstrated to play a role in regulation of herpesviral infectious cycle, such as infection with human cytomeg alovirus (HCMV). About 30,000 children each year are born with congenital CMV infection, and more than 5,000 suffer from permanent health problems associated with it. Due to the absence of effective therapeutics and vaccines, HCMV has a major impact on public health. In this study, we used interdisciplinary approach integrating virology, proteomics, and bioinformatics in order to elucidate the pathways involved in regulation of HCMV infection in SIRT1 and SIRT2 -dependent manner.