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A conserved methyltransferase active site residue of Zika virus NS5 is required for the restriction of STING activation and interferon expression.
Li, Yuting; Li, Zhaoxin; Zou, Haimei; Zhou, Peiwen; Huo, Yuhang; Fan, Yaohua; Liu, Xiaohong; Wu, Jianguo; Li, Geng; Wang, Xiao.
Afiliação
  • Li Y; Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
  • Li Z; Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
  • Zou H; The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China.
  • Zhou P; Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, Guangdong, PR China.
  • Huo Y; Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
  • Fan Y; First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
  • Liu X; First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
  • Wu J; Guangdong Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, Guangdong, PR China.
  • Li G; Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
  • Wang X; Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong, PR China.
J Gen Virol ; 105(2)2024 02.
Article em En | MEDLINE | ID: mdl-38299799
ABSTRACT
Zika virus (ZIKV) is a re-emerging RNA virus and causes major public health events due to its link to severe neurological complications in foetuses and neonates. The cGAS-STING signalling pathway regulates innate immunity and plays an important role in the invasion of DNA and RNA viruses. This study reveals a distinct mechanism by which ZIKV restricts the cGAS-STING signalling to repress IFN-ß expression. ZIKV attenuates IFN-ß expression induced by DNA viruses (herpes simplex virus type 1, HSV-1) or two double-stranded DNAs (dsDNA90 and HSV120) in mouse embryonic fibroblasts (MEFs). Notably, ZIKV NS5, the viral RNA-dependent RNA polymerase, was responsible for the repression of IFN-ß. NS5 interacts with STING in the cytoplasm, suppresses IRF3 phosphorylation and nucleus localization and promotes the cleavage of STING K48-linked polyubiquitination. Furthermore, the NS5 methyltransferase (MTase) domain interacts with STING to restrict STING-induced IFN-ß expression. Interestingly, point mutation analyses of conserved methyltransferase active site residue D146 indicate that it is critical for repressing IFN-ß expression induced by STING stimulation in cGAS-STING signalling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Zika virus / Infecção por Zika virus Limite: Animals Idioma: En Revista: J Gen Virol Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Zika virus / Infecção por Zika virus Limite: Animals Idioma: En Revista: J Gen Virol Ano de publicação: 2024 Tipo de documento: Article