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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 11, 2013
Respiratory syncytial virus infections: old challenges and new opportunities
Asunción Mejías1, Susana Chávez-Bueno, Hasan S Jafri
1Division of Pediatric Infectious Diseases, The University of Texas Southwestern Medical Center and Children's Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Insights
Respiratory syncytial virus (RSV) causes severe lung inflammation and mucus overproduction in mice, leading to long-term airway disease. This mouse model aids in understanding RSV immunopathogenesis and developing new treatments and vaccines.
Area of Science:
- Immunology
- Virology
- Pulmonology
Background:
- Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants.
- RSV infections can cause severe disease in the elderly and immunocompromised individuals.
- The virus causes recurrent infections throughout life, posing a significant public health burden.
Purpose of the Study:
- To investigate the immunopathogenesis of RSV infection using a mouse model.
- To examine acute and chronic disease phases, including airway obstruction and hyperresponsiveness.
- To summarize novel treatment and prevention strategies for RSV.
Main Methods:
- Utilized a mouse model of RSV infection.
- Measured airway obstruction via enhanced pause in the acute phase.
- Assessed airway hyperresponsiveness using methacholine challenge in the chronic phase.
Main Results:
- RSV-infected mice showed progressive pneumonia with increased histopathologic scores.
- Acute RSV infection led to mucus overproduction, evidenced by hypertrophic cells.
- Chronic infection resulted in persistent airway hyperresponsiveness and inflammation.
Conclusions:
- RSV infection in mice leads to chronic inflammatory changes and mucus overproduction, contributing to long-term airway disease.
- Findings correlate histologic changes with pulmonary responses measured by plethysmography.
- Ongoing clinical trials show promise for new RSV vaccines and treatments.
Background:
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia among children aged < 1 year. The majority of children hospitalized for RSV infection are younger than 6 months of age. RSV also causes repeated infections including severe lower respiratory tract disease, which may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems.
Methods:
Using the mouse model of RSV infection, this article examines the immunopathogenesis during acute and chronic phases of the disease. This model allows for measurement of basal enhanced pause, which reflects airway obstruction in the acute phase, and the response to methacholine challenge to assess airway hyperresponsiveness during the chronic phase. This article also summarizes some recent studies focusing on novel perspectives and strategies for treatment and prevention of RSV infections.
Results:
Compared with the lungs of sham-inoculated control mice, mice inoculated with live RSV showed a persistent progression of the severity of pneumonia as determined by an increasing histopathologic score. Mucus production of RSV-infected mice in the acute phase illustrated increased periodic acid-Schiff-positive hypertrophic cells in central and peripheral airways.
Conclusions:
RSV-infected mice with persistent airway hyperresponsiveness exhibited the presence of abnormal chronic inflammatory changes and mucus overproduction, which likely contributed to long term airway disease induced by RSV infection. These findings provide a histologic correlation to the abnormal pulmonary responses documented by plethysmography. Current trials have demonstrated positive results in continuing to target different alternatives for a new RSV vaccine.
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