Langat virus inhibits the gp130/JAK/STAT signaling by reducing the gp130 protein level

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medical virology 2024-04, Vol.96 (4), p.e29522-n/a
Main Authors: Lin, Shaoli, Wang, Xiaochun, Sallapalli, Bhargava Teja, Hage, Adam, Chang, Peixi, He, Jia, Best, Sonja M., Zhang, Yanjin
Format: Article
Language:English
Subjects:
Biological activity
Cell interactions
Drug development
Encephalitis
Glycoprotein gp130
gp130
Infections
Invasiveness
JAK/STAT signaling
Janus kinase
Kinases
Langat virus (LGTV)
NS5
NS5 protein
Nuclear transport
Oncostatin M
Pathogenesis
Proteins
signal transducer and activator of transcription 3 (STAT3)
Stat1 protein
Stat2 protein
Stat3 protein
Tick-borne encephalitis
tick‐borne encephalitis virus (TBEV)
Translocation
Vero cells
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0146-6615
1096-9071
DOI:10.1002/jmv.29522