New mouse model of pulmonary hypertension induced by respiratory syncytial virus bronchiolitis
Related Experiment Video
Updated: Feb 8, 2026
Generation and Assembly of Virus-Specific Nucleocapsids of the Respiratory Syncytial Virus
Published on: July 27, 2021
Dai Kimura1, Jordy Saravia1,2, Sridhar Jaligama1,3
1Department of Pediatrics, University of Tennessee Health Science Center, Children's Foundation Research Institute, Le Bonheur Children's Hospital , Memphis, Tennessee.
Insights
Researchers developed a new mouse model for respiratory syncytial virus (RSV)-induced pulmonary hypertension (PH). This model mimics infant disease, aiding research into PH causes and treatments.
Area of Science:
- Pediatric Respiratory Medicine
- Cardiovascular Physiology
- Infectious Disease Immunology
Background:
- Infants with respiratory syncytial virus (RSV) bronchiolitis can develop pulmonary hypertension (PH), increasing morbidity and mortality, especially in those with congenital heart disease.
- Current understanding of RSV-induced PH pathogenesis and effective treatments is limited due to a lack of appropriate preclinical models.
Purpose of the Study:
- To establish and validate a novel mouse model that accurately replicates the etiology of pulmonary hypertension secondary to respiratory syncytial virus bronchiolitis in infants.
- To utilize this model for investigating the underlying molecular mechanisms and evaluating potential therapeutic interventions for this condition.
Main Methods:
- Neonatal mice were infected with RSV and subsequently reinfected to mimic disease progression.
- Pulmonary hypertension was assessed using echocardiography (measuring pulmonary artery acceleration time and acceleration time-to-ejection time ratio) and right ventricular systolic pressure (RVSP) measurements.
- Pulmonary artery structural changes, including medial wall thickness and degree of muscularization, were analyzed via morphometry.
Main Results:
- RSV-infected mice exhibited significantly elevated RVSP compared to control groups.
- Echocardiography revealed a shortened pulmonary artery acceleration time and a decreased acceleration time-to-ejection time ratio in RSV-infected mice, indicative of PH.
- Morphometric analysis demonstrated increased pulmonary artery medial wall thickness and a higher number of muscularized pulmonary arteries in RSV-infected mice.
Conclusions:
- The developed mouse model successfully recapitulates key features of pulmonary hypertension secondary to RSV bronchiolitis observed in human infants.
- This model provides a valuable platform for dissecting the molecular pathways involved in RSV-induced PH and for preclinical testing of novel therapeutic strategies.
- This represents the first established mouse model for RSV-induced pulmonary hypertension, opening new avenues for research in this critical area.
Abstract:
Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of the present study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age and then reinfected 4 wk later. Serum-free medium was administered to age-matched mice as a control. Echocardiography and right ventricular systolic pressure (RVSP) measurements via right jugular vein catheterization were conducted 5 and 6 days after the second infection, respectively. Peripheral capillary oxygen saturation monitoring did not indicate hypoxia at 2-4 days post-RSV infection, before reinfection, and at 2-7 days after reinfection. RSV-infected mice had significantly higher RVSP than control mice. Pulsed-wave Doppler recording of the pulmonary blood flow by echocardiogram demonstrated a significantly shortened pulmonary artery acceleration time and decreased pulmonary artery acceleration time-to-ejection time ratio in RSV-infected mice. Morphometry showed that RSV-infected mice exhibited a significantly higher pulmonary artery medial wall thickness and had an increased number of muscularized pulmonary arteries compared with control mice. These findings, confirmed by RVSP measurements, demonstrate the development of PH in the lungs of mice infected with RSV as neonates. This animal model can be used to study the pathogenesis of PH secondary to RSV bronchiolitis and to assess the effect of treatment interventions. NEW & NOTEWORTHY This is the first mouse model of respiratory syncytial virus-induced pulmonary hypertension, to our knowledge. This model will allow us to decipher molecular mechanisms responsible for the pathogenesis of pulmonary hypertension secondary to respiratory syncytial virus bronchiolitis with the use of knockout and/or transgenic animals and to monitor therapeutic effects with echocardiography.
Related Concept Videos
01:16Treatment for Pulmonary Arterial Hypertension: Oxygen Therapy for Respiratory Failure
Oxygen therapy is vital in increasing and maintaining blood oxygen levels in PAH patients. As a result, it aids in reducing fatigue,...
01:30Pulmonary Hypertension: Classification and Pathogenesis
There are various classifications for PH, each relating to different underlying causes and also...
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:13Induced-fit Model
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...