Proteins of the secretory pathway govern virus productivity during lytic gammaherpesvirus infection

J Mages1, K Freimüller, R Lang

  • 1Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany.

Abstract

Insights

Targeting host cell secretory pathway proteins, Lman1 and synaptobrevin-like 1, significantly reduces gammaherpesvirus production. This offers a promising alternative to traditional antiviral drugs for combating viral infections.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Gammaherpesvirus infections pose significant health challenges.
  • Antiviral drugs targeting viral products face resistance issues.
  • Host cell targets offer an alternative therapeutic strategy.

Purpose of the Study:

  • To identify host cell genes and pathways crucial for gammaherpesvirus replication.
  • To explore potential new antiviral targets within the host cell.

Main Methods:

  • Infection of fibroblasts, endothelial precursor cells, and macrophages with murine gammaherpesvirus.
  • Oligonucleotide microarrays to analyze host cell transcriptional response.
  • Modulation of specific gene functions (Lman1, sybl1) to assess impact on viral production.

Main Results:

  • Two host genes, Lman1 and synaptobrevin-like 1 (sybl1), were significantly upregulated across all tested cell types post-infection.
  • These proteins are involved in cellular exocytosis and glycoprotein transport.
  • Inhibiting Lman1 or sybl1 function markedly reduced gammaherpesvirus production.

Conclusions:

  • Host cell secretory pathway proteins can be rate-limiting for gammaherpesvirus production.
  • Lman1 and sybl1 represent potential novel targets for antiviral interventions against gammaherpesviruses.

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