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Updated: Jun 29, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Langat virus inhibits the gp130/JAK/STAT signaling by reducing the gp130 protein level

Shaoli Lin1, Xiaochun Wang1, Bhargava Teja Sallapalli1

  • 1Molecular Virology Laboratory, Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, MD, USA.

Journal of Medical Virology
|March 27, 2024
PubMed

Insights

Langat virus (LGTV) and tick-borne encephalitis virus (TBEV) inhibit gp130/JAK/STAT signaling pathways. This viral interference impacts host cell responses and offers targets for novel antiviral therapies and vaccines.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Tick-borne encephalitis virus (TBEV) serocomplex causes severe neuroinvasive diseases.
  • Langat virus (LGTV), a TBEV relative, models virus-host interactions with lower pathogenicity.
  • gp130/JAK/STAT signaling is crucial for biological processes and immune responses.

Purpose of the Study:

  • To investigate the effect of LGTV infection on gp130/JAK/STAT signaling.
  • To elucidate the role of viral proteins in modulating this pathway.
  • To explore potential antiviral strategies based on these interactions.

Main Methods:

  • Assessing STAT3 phosphorylation and nuclear translocation in LGTV-infected cells stimulated with oncostatin M (OSM).
  • Measuring JAK1 activation and gp130 protein expression in infected cells.
  • Evaluating the impact of LGTV NS5 protein and TBEV infection on gp130 levels.
  • Investigating the antiviral effects of OSM pretreatment and the role of STAT1/STAT2.

Main Results:

  • LGTV infection significantly reduced phosphorylated STAT3 (pSTAT3) levels and blocked STAT3 nuclear translocation upon OSM stimulation.
  • LGTV inhibited JAK1 activation and decreased gp130 expression, mediated by the viral NS5 protein.
  • TBEV infection also led to reduced gp130 levels.
  • OSM pretreatment inhibited LGTV replication, suggesting a STAT3-mediated antiviral mechanism independent of STAT1/STAT2.

Conclusions:

  • LGTV and TBEV interfere with the gp130/JAK/STAT signaling pathway.
  • The viral NS5 protein plays a role in downregulating gp130 expression.
  • OSM-induced antiviral effects appear to be mediated by STAT3 signaling.
  • Understanding these virus-host interactions provides a basis for developing new antiviral treatments and vaccines against TBEV and related flaviviruses.
Keywords:
JAK/STAT signalingLangat virus (LGTV)NS5gp130signal transducer and activator of transcription 3 (STAT3)tick‐borne encephalitis virus (TBEV)

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