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Updated: Nov 7, 2025
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Slow viral propagation during initial phase of infection leads to viral persistence in mice
Haifeng C Xu1, Ruifeng Wang1, Prashant V Shinde1
1Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Abstract:
Immune evasion of pathogens can modify the course of infection and impact viral persistence and pathology. Here, using different strains of the lymphocytic choriomeningitis virus (LCMV) model system, we show that slower propagation results in limited type I interferon (IFN-I) production and viral persistence. Specifically, cells infected with LCMV-Docile exhibited reduced viral replication when compared to LCMV-WE and as a consequence, infection with LCMV-Docile resulted in reduced activation of bone marrow derived dendritic cells (BMDCs) and IFN-I production in vitro in comparison with LCMV-WE. In vivo, we observed a reduction of IFN-I, T cell exhaustion and viral persistence following infection of LCMV-Docile but not LCMV-WE. Mechanistically, block of intracellular protein transport uncovered reduced propagation of LCMV-Docile when compared to LCMV-WE. This reduced propagation was critical in blunting the activation of the innate and adaptive immune system. When mice were simultaneously infected with LCMV-Docile and LCMV-WE, immune function was restored and IFN-I production, T cell effector functions as well as viral loads were similar to that of mice infected with LCMV-WE alone. Taken together, this study suggests that reduced viral propagation can result in immune evasion and viral persistence.
Insights
Slower viral replication, like with lymphocytic choriomeningitis virus (LCMV)-Docile, leads to immune evasion and viral persistence by limiting type I interferon (IFN-I) production. Co-infection restores immune function.
Area of Science:
- Immunology
- Virology
- Pathogen-host interactions
Background:
- Pathogen immune evasion influences infection outcomes, viral persistence, and disease.
- Type I interferons (IFN-I) are crucial in antiviral defense.
- Lymphocytic choriomeningitis virus (LCMV) is a model for studying host-pathogen dynamics.
Purpose of the Study:
- To investigate how viral propagation rate affects immune responses and persistence.
- To elucidate the mechanisms by which slower viral spread influences immune evasion.
Main Methods:
- Comparative analysis of LCMV strains (LCMV-Docile vs. LCMV-WE) in vitro and in vivo.
- Assessment of viral replication, immune cell activation (BMDCs), IFN-I production, and T cell exhaustion.
- In vivo studies using mouse models, including simultaneous co-infection experiments.
- Investigation of intracellular protein transport to understand viral propagation differences.
Main Results:
- LCMV-Docile exhibited reduced replication compared to LCMV-WE, leading to lower IFN-I production and BMDC activation in vitro.
- In vivo, LCMV-Docile infection resulted in reduced IFN-I levels, T cell exhaustion, and viral persistence.
- Impaired intracellular protein transport was linked to the reduced propagation of LCMV-Docile.
- Simultaneous infection with both LCMV strains restored immune function, IFN-I production, T cell responses, and viral loads to levels seen with LCMV-WE alone.
Conclusions:
- Reduced viral propagation is a mechanism for immune evasion, promoting viral persistence.
- Viral spread rate critically impacts the host's innate and adaptive immune system activation.
- Modulating viral replication dynamics can alter the course of infection and immune response.
