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Updated: May 29, 2026
A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019
Selection of rhinovirus 1A variants adapted for growth in mouse lung epithelial cells
Angela L Rasmussen1, Vincent R Racaniello
1Department of Microbiology, University of Washington, Seattle, WA 98114, USA. arasmus@u.washington.edu
Abstract:
Rhinoviruses (RVs) are picornaviruses that are causative agents of the majority of upper respiratory tract infections, or "common colds," in humans. RVs infect both the upper and lower respiratory tract, and in addition to the common cold may also cause pneumonia, complications in patients with chronic lung diseases such as cystic fibrosis, and asthma exacerbations. Convenient animal models are not available to study the pathogenesis of rhinovirus-induced illness. Rhinovirus RV1A replicates poorly in mouse cells; variants with improved replication were selected by serial passage through mouse embryonic fibroblasts and mouse lung epithelial cells. Adaptation for improved growth in mouse cells was mediated by amino acid changes in the RV1a non-structural protein 3A. Mouse cell-adapted RV1A was capable of productively infecting mice in which the airway was subjected to chemical permeabilization. A mouse model for RV infection will permit studies of RV pathogenesis and may identify targets for therapeutic intervention.
Insights
Researchers developed a mouse model for rhinovirus (RV) infection, the cause of the common cold. This new model, using adapted RV1A, will aid in studying RV pathogenesis and finding new treatments.
Area of Science:
- Virology
- Immunology
- Respiratory Medicine
Background:
- Rhinoviruses (RVs) are the primary cause of human upper respiratory tract infections, commonly known as the "common cold."
- RVs can also lead to more severe conditions like pneumonia, asthma exacerbations, and complications in cystic fibrosis patients.
- Current limitations exist due to the lack of suitable animal models for studying RV pathogenesis.
Purpose of the Study:
- To develop a functional animal model for rhinovirus infection to study disease mechanisms.
- To investigate the potential of adapted RV strains for use in a mouse model.
- To identify potential therapeutic targets for rhinovirus-induced illnesses.
Main Methods:
- Rhinovirus RV1A was adapted for improved replication in mouse embryonic fibroblasts and lung epithelial cells through serial passage.
- Amino acid alterations in the non-structural protein 3A were identified as key to this adaptation.
- Mouse model development involved productively infecting mice with adapted RV1A after chemical permeabilization of the airway.
Main Results:
- Rhinovirus RV1A variants with enhanced replication in mouse cells were successfully generated.
- Specific amino acid changes in RV1A protein 3A were crucial for improved mouse cell adaptation.
- Adapted RV1A demonstrated productive infection in mice with a permeabilized airway.
Conclusions:
- A novel mouse model for rhinovirus infection has been established.
- This model provides a valuable tool for investigating rhinovirus pathogenesis and host response.
- The developed model may facilitate the identification of new therapeutic strategies against rhinovirus infections.
