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Updated: Jul 16, 2026
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus
Rui Xiong1,2, Rui Fu1, Yong Wu1
1National Rodent Laboratory Animal Resources Center, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China.
Abstract:
Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR/Cas9 technology. Rag2-/- mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 109.8 copies/g and 1c106 TCID50 in nasal cavity, as well as 1 × 108 copies/g and 1 × 105 TCID50 in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2-/- mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2-/- mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics.
Insights
A new Rag2 knockout mouse model enables sustained human respiratory syncytial virus (hRSV) infection. This model supports studying hRSV pathogenesis and evaluating therapeutics, overcoming limitations of previous animal models.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Existing animal models for human respiratory syncytial virus (hRSV) have limitations in permissiveness and infection duration.
- These limitations hinder research into hRSV pathogenesis and the development of effective therapeutics.
Purpose of the Study:
- To develop a novel mouse model for studying hRSV infection and disease.
- To overcome the limitations of existing animal models for hRSV research.
Main Methods:
- Utilized CRISPR/Cas9 gene editing technology to create Rag2 knockout (Rag2-/-) mice.
- Intranasal inoculation of Rag2-/- mice with hRSV to establish infection.
- Assessed viral loads, pathological changes, immune responses, and therapeutic efficacy.
Main Results:
- Rag2-/- mice exhibited high and sustained viral loads in the nasal cavity and lungs for up to 5 weeks.
- Observed mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines, and increased NK cells in infected Rag2-/- mice.
- A humanized monoclonal antibody demonstrated significant antiviral activity in this model.
Conclusions:
- Rag2-/- mice provide a robust platform for long-term, stable hRSV infection.
- This model is valuable for investigating hRSV transmission and pathogenesis.
- The model serves as an effective tool for evaluating the efficacy of antiviral therapeutics against hRSV.
