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YAP inhibits HCMV replication by impairing STING-mediated nuclear transport of the viral genome.
Lee, Ju Hyun; Kwon, Mookwang; Lim, Woo Young; Yoo, Chae Rin; Yoon, Youngik; Han, Dasol; Ahn, Jin-Hyun; Yoon, Keejung.
Afiliação
  • Lee JH; Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, South Korea.
  • Kwon M; College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.
  • Lim WY; Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, South Korea.
  • Yoo CR; Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, South Korea.
  • Yoon Y; Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, South Korea.
  • Han D; College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, South Korea.
  • Ahn JH; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Sungkyunkwan University, Suwon, South Korea.
  • Yoon K; Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, South Korea.
PLoS Pathog ; 18(12): e1011007, 2022 12.
Article em En | MEDLINE | ID: mdl-36455047
ABSTRACT
YES-associated protein (YAP), a critical actor of the mammalian Hippo signaling pathway involved in diverse biological events, has gained increased recognition as a cellular factor regulated by viral infections, but very few studies have investigated their relationship vice versa. In this study, we show that YAP impairs HCMV replication as assessed by viral gene expression analysis and progeny assays, and that this inhibition occurs at the immediate-early stages of the viral life cycle, at the latest. Using YAP mutants lacking key functional domains and shRNA against TEAD, we show that the inhibitory effects of YAP on HCMV replication are nuclear localization- and TEAD cofactor-dependent. Quantitative real-time PCR (qPCR) and subcellular fractionation analyses reveal that YAP does not interfere with the viral entry process but inhibits transport of the HCMV genome into the nucleus. Most importantly, we show that the expression of stimulator of interferon genes (STING), recently identified as an important component for nuclear delivery of the herpesvirus genome, is severely downregulated by YAP at the level of gene transcription. The functional importance of STING is further confirmed by the observation that STING expression restores YAP-attenuated nuclear transport of the HCMV genome, viral gene expression, and progeny virus production. We also show that HCMV-upregulated YAP reduces expression of STING. Taken together, these findings indicate that YAP possesses both direct and indirect regulatory roles in HCMV replication at different infection stages.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Replicação Viral / Citomegalovirus Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Replicação Viral / Citomegalovirus Idioma: En Ano de publicação: 2022 Tipo de documento: Article