STING facilitates nuclear import of herpesvirus genome during infection

Yujin Hong, Heena Jeong, Kiwon Park, Sungwon Lee, Jae Youn Shim, Hyewon Kim, Yang Song, Seowoo Park, Hye Yoon Park, V. Narry Kim, Kwangseog Ahn

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Once inside the host cell, DNA viruses must overcome the physical barrier posed by the nuclear envelope to establish a successful infection. The mechanism underlying this process remains unclear. Here, we show that the herpesvirus exploits the immune adaptor stimulator of interferon genes (STING) to facilitate nuclear import of the viral genome. Following the entry of the viral capsid into the cell, STING binds the viral capsid, mediates capsid docking to the nuclear pore complex via physical interaction, and subsequently enables accumulation of the viral genome in the nucleus. Silencing STING in human cytomegalovirus (HCMV)-susceptible cells inhibited nuclear import of the viral genome and reduced the ensuing viral gene expression. Overexpressing STING increased the host cell's susceptibility to HCMV and herpes simplex virus 1 by improving the nuclear delivery of viral DNA at the early stage of infection. These observations suggest that the proviral activity of STING is conserved and exploited by the herpesvirus family. Intriguingly, in monocytes, which act as latent reservoirs of HCMV, STING deficiency negatively regulated the establishment of HCMV latency and reactivation. Our findings identify STING as a proviral host factor regulating latency and reactivation of herpesviruses.

Original languageEnglish (US)
Article numbere2108631118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number33
DOIs
StatePublished - Aug 17 2021
Externally publishedYes

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We are grateful to William Britt at the University of Alabama at Birmingham for providing the anti-MCP (UL86) antibody. We would like to thank the members of the K.A. Laboratory for their helpful discussions and technical assistance. This work was supported by a National Research Foundation (NRF) grant funded by the Korea Ministry of Science and ICT (MSIT) (0409-20200207) and Grant IBS-R008-D1 from the Institute for Basic Science (IBS) of the MSIT (to K.A.). The Global PhD Fellowship Program through the NRF of Korea is funded by the Ministry of Education (2012-015863 to Y.H.), the China Scholarship Council (201806220081 to Y.S.), and BK21 Research Fellowships from the Ministry of Education of Korea (to Y.H., H.J., K.P., S.L., and H.K.).

Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.

Keywords

  • Cell susceptibility
  • HCMV
  • Nuclear import
  • STING

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