Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain

Abstract

Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects, represents a serious complication for immunocompromised HIV/AIDS and organ transplant patients, and contributes to both immunosenescence and cardiovascular diseases. HCMV is also implicated in cancers such as glioblastoma multiforme (GBM) and infects ex vivo -cultured GBM tumor cells. In dividing tumor cells, the genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis. This mitotic survival is mediated by a viral protein with a chromatin-tethering domain (CTD). Here, we report that the HCMV genome is maintained in dividing fibroblasts by the CTD of the viral IE19 protein. The discovery of a viral genome maintenance factor during productive infection could help explain viral genome dynamics within HCMV-positive tumors as well as during latency.