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Langat virus inhibits the gp130/JAK/STAT signaling by reducing the gp130 protein level.
Lin, Shaoli; Wang, Xiaochun; Sallapalli, Bhargava Teja; Hage, Adam; Chang, Peixi; He, Jia; Best, Sonja M; Zhang, Yanjin.
Afiliação
  • Lin S; Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
  • Wang X; Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
  • Sallapalli BT; Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
  • Hage A; Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
  • Chang P; Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
  • He J; Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
  • Best SM; Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
  • Zhang Y; Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.
J Med Virol ; 96(4): e29522, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38533889
ABSTRACT
The tick-borne encephalitis virus (TBEV) serocomplex includes several medically important flavivirus members endemic to Europe, Asia, and North America, which can induce severe neuroinvasive or viscerotropic diseases with unclear mechanisms of pathogenesis. Langat virus (LGTV) shares a high sequence identity with TBEV but exhibits lower pathogenic potential in humans and serves as a model for virus-host interactions. In this study, we demonstrated that LGTV infection inhibits the activation of gp130/JAK/STAT (Janus kinases (JAK) and signal transducer and activator of transcription (STAT)) signaling, which plays a pivotal role in numerous biological processes. Our data show that the LGTV-infected cells had significantly lower phosphorylated STAT3 (pSTAT3) protein upon oncostatin M (OSM) stimulation than the mock-infected control. LGTV infection blocked the nuclear translocation of STAT3 without a significant effect on total STAT3 protein level. LGTV inhibited JAK1 activation and reduced gp130 protein expression in infected cells, with the viral NS5 protein mediating this effect. TBEV infection also reduces gp130 level. On the other hand, pretreatment of Vero cells with OSM significantly reduces LGTV replication, and STAT1/STAT2 knockdown had little effect on OSM-mediated antiviral effect, which suggests it is independent of STAT1/STAT2 and, instead, it is potentially mediated by STAT3 signlaing. These findings shed light on the LGTV and TBEV-cell interactions, offering insights for the future development of antiviral therapeutics and improved vaccines.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenômenos Biológicos / Vírus da Encefalite Transmitidos por Carrapatos Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenômenos Biológicos / Vírus da Encefalite Transmitidos por Carrapatos Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article