Related Experiment Video
Updated: Jul 10, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Enabled interferon signaling evasion in an immune-competent transgenic mouse model of parainfluenza virus 5 infection
Thomas A Kraus1, Lily Garza, Curt M Horvath
1Department of Medicine, Northwestern University, Evanston, IL 60208, USA. t-kraus@northwestern.edu
Abstract:
Parainfluenza virus 5 (PIV5 or SV5) infects several mammalian species but is restricted from efficient replication in mice. In humans, PIV5 evades IFN signaling by targeting STAT1 for proteasomal degradation in a STAT2-dependent reaction. In contrast, cell culture experiments have demonstrated that the divergent murine STAT2 protein fails to support STAT1 targeting. Expression of human STAT2 in mouse cells can overcome the species restriction to enable PIV5-induced STAT1 degradation and subsequent IFN antagonism. Here, we describe a transgenic mouse that ubiquitously expresses human STAT2. PIV5 infection induces STAT1 degradation leading to enhanced virus replication and protein expression in the cells from the transgenic mouse but not from the non-transgenic littermates. Importantly, intranasal inoculation with PIV5 results in increased viral load in the lungs of the transgenic mice compared to wild-type littermates. These transgenic mice provide a small animal model to study the role of innate immune evasion in paramyxovirus pathogenesis.
Insights
Transgenic mice expressing human STAT2 enable Parainfluenza virus 5 (PIV5) to degrade STAT1, enhancing viral replication. This model aids studying paramyxovirus pathogenesis and innate immune evasion.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Parainfluenza virus 5 (PIV5) infects many mammals but replicates poorly in mice.
- PIV5 evades human interferon (IFN) signaling by degrading STAT1 via a STAT2-dependent pathway.
- Murine STAT2 does not support STAT1 degradation, contributing to species-specific PIV5 replication restriction.
Purpose of the Study:
- To investigate the role of STAT2 in PIV5 species restriction.
- To develop a mouse model for studying PIV5 pathogenesis and innate immune evasion.
Main Methods:
- Generation of transgenic mice ubiquitously expressing human STAT2.
- Infection of transgenic and wild-type mice with PIV5.
- Analysis of STAT1 degradation, viral replication, and viral load in lung tissue.
Main Results:
- PIV5 infection induced STAT1 degradation in cells from human STAT2 transgenic mice.
- Transgenic mice exhibited enhanced PIV5 replication and protein expression compared to non-transgenic littermates.
- Intranasal PIV5 inoculation led to increased viral load in the lungs of transgenic mice.
Conclusions:
- Human STAT2 expression in mice overcomes PIV5 species restriction by enabling STAT1 degradation.
- These transgenic mice serve as a valuable model for studying paramyxovirus innate immune evasion and pathogenesis.
