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Updated: Jul 8, 2026

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
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.
Background:
Diseases caused by gammaherpesviruses continue to be a challenge for human health and antiviral treatment. Most of the commonly used antiviral drugs are directed against viral gene products. However, the emergence of drug-resistant mutations ma limit the effectiveness of these drugs. Since viruses require a host cell to propagate, the search for host cell targets is an interesting alternative.
Methods:
In this study, we infected three different cell types (fibroblasts, endothelial precursor cells and macrophages with a murine gammaherpesvirus and analysed the host cell response for changes either common to all or unique to a particular cell type using oligonucleotide microarrays.
Results:
The analysis revealed a number of genes whose transcription was significantly up- or down-regulated in either one or two of the cell types tested. After infection, only two genes, Lman1 (also known as ERGIC53) an synaptobrevin-like 1 (sybl1) were significantly up-regulated in all three cell types, suggestive for a general role for the virus life cycl independent of the cell type. Both proteins have been implicated in cellular exocytosis and transport of glycoproteins through the secretory pathway. To test the significance of the observed up-regulation, the functionality of these proteins was modulated, and the effect on virus replication was monitored. Inhibition of either Lman1 or sybl1 resulted in a significant reduction in virus production.
Conclusions:
This suggests that proteins of the secretory pathway which appear to be rate limiting for virus production may represent new targets for intervention.
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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