Respiratory Syncytial Virus (RSV) RNA loads in peripheral blood correlates with disease severity in mice

Juan Pablo Torres,Asuncion Mejias,Claudia Tagliabue,Ana M Gomez,Shama Khokhar,Vijay G Bhoj,Peter A Kiener,Michael L Chang,Octavio Ramilo,Paula A Revell

doi:10.1186/1465-9921-11-125

Abstract

BackgroundRespiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity.MethodsBalb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood.ResultsRSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes.ConclusionsRSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.

Highlights

Respiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium
In mice infected with live RSV, RSV RNA loads measured in whole lung and brochoalveolar lavage (BAL) samples were comparable and significantly higher than RSV RNA loads measured in nasal wash samples from day 1 to 10 post-inoculation
By day 10, RSV RNA was no longer detected in nasal wash specimens but remained significantly elevated in whole lung samples until day 21 post inoculation (Fig. 1A)

Summary

Introduction

Respiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, there is no consistent information whether virus detection in the blood correlates with disease severity. The clinical manifestations of the disease are thought to be a result of the direct viral cytopathic effect on the respiratory epithelium and the host immune response leading to significant inflammation of the respiratory tract [3,4,5,6]. We determined 1) whether RSV could be detected in peripheral blood during the acute phase of the disease, 2) its time course of detection compared with the upper and lower respiratory tract, and 3) whether the RSV-induced systemic cytokine response and clinical parameters of disease severity (airway obstruction and lung inflammation) were correlated with blood RSV RNA loads

Methods

Results

Conclusion