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Human cytomegalovirus genomes survive mitosis via the IE19 chromatin-tethering domain

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Lyon_2020_mBio_humancytomegalovirus_VoR_CCBY.pdf (3.017Mb)
Date
09/2020
Author
Lyon, Shelby M.
Yetming, Kristen D.
Paulus, Christina
Nevels, Michael
Kalejta, Robert F.
Keywords
Cancer
Chromatin
Herpes
Latency
Mitosis
Transcription
QH426 Genetics
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
NDAS
Metadata
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Abstract
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.
Citation
Lyon , S M , Yetming , K D , Paulus , C , Nevels , M , Kalejta , R F & Schultz-cherry , S (ed.) 2020 , ' Human cytomegalovirus genomes survive mitosis via the IE19 chromatin-tethering domain ' , mBio , vol. 11 , no. 5 , e02410-20 . https://doi.org/10.1128/mBio.02410-20
Publication
mBio
Status
Peer reviewed
DOI
https://doi.org/10.1128/mBio.02410-20
ISSN
2150-7511
Type
Journal article
Rights
Copyright © 2020 Lyon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Description
This work was supported by NIH grants AI139180 and AI130089 to R.F.K. S.M.L. was supported by NRSA award T32 CA009135.
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/20787

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