Human Cytomegalovirus Genomes Survive Mitosis via the IE19 Chromatin-Tethering Domain.
Shelby M LyonKristen D YetmingChristina PaulusMichael M NevelsRobert F KalejtaPublished in: mBio (2020)
The genomes of DNA tumor viruses regain nuclear localization after nuclear envelope breakdown during mitosis through the action of a viral protein with a chromatin-tethering domain (CTD). Here, we report that the human cytomegalovirus (HCMV) genome is maintained during mitosis by the CTD of the viral IE19 protein. Deletion of the IE19 CTD or disruption of the IE19 splice acceptor site reduced viral genome maintenance and progeny virion formation during infection of dividing fibroblasts, both of which were rescued by IE19 ectopic expression. The discovery of a viral genome maintenance factor during productive infection provides new insight into the mode of HCMV infection implicated in birth defects, organ transplant failure, and cancer.IMPORTANCE 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.
Keyphrases
- sars cov
- endothelial cells
- genome wide
- hiv aids
- gene expression
- small molecule
- transcription factor
- dna damage
- protein protein
- end stage renal disease
- binding protein
- high throughput
- chronic kidney disease
- cell free
- amino acid
- ejection fraction
- intensive care unit
- human immunodeficiency virus
- coronary artery disease
- newly diagnosed
- antiretroviral therapy
- pregnant women
- peritoneal dialysis
- single cell
- prognostic factors
- cardiovascular events
- squamous cell