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STING facilitates nuclear import of herpesvirus genome during infection

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Title
STING facilitates nuclear import of herpesvirus genome during infection
Author(s)
Yujin Hong; Heena Jeong; Kiwon Park; Sungwon Lee; Shim, Jae Youn; Hyewon Kim; Yang Song; Seowoo Park; Park, Hye Yoon; V. Narry Kim; Kwangseog Ahn
Subject
HUMAN CYTOMEGALOVIRUS-INFECTION, ; HOST-CELL PERMISSIVENESS, ; PORE COMPLEX, ; VIRUS, ; STIMULATOR, ; MECHANISM, ; PATHWAY, ; DISEASE, ; BINDING
Publication Date
2021-08-17
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.118, no.33
Publisher
National Academy of Sciences
Abstract
© 2021 National Academy of Sciences. All rights reserved.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.
URI
https://pr.ibs.re.kr/handle/8788114/10176
DOI
10.1073/pnas.2108631118
ISSN
0027-8424
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
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