Replication and Clearance of Respiratory Syncytial Virus

Abstract

Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus and the infections with human respiratory syncytial virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared by neutrophils whereas apoptosis was an important way of clearance of BRSV-infected epithelial cells. Neighboring cells, which probably were epithelial cells, phagocytized the BRSV-infected apoptotic cells. The number of both CD4(+) and CD8+ T cells increased during the course of infection, but the T cells were not found between the epithelial cells of the bronchi up until apoptosis was no longer detected, thus in the bronchi there was no indication of direct contact-dependent T-cell-mediated cytotoxicity in the primary infection.

Synthetic Biodegradable Microparticle and Nanoparticle Vaccines against the Respiratory Syncytial Virus

“…RSV infection takes place initially in the ciliated columnar cells of the URT, and then, it spreads to the LRT largely by aspiration of virus-containing secretion into the trachea and by direct cell-to-cell spread [23]. RSV inhibits cilial beat and induces loss of cilia from the epithelial surface [16].…”

“…RSV inhibits cilial beat and induces loss of cilia from the epithelial surface [16]. Studies in calves infected with bovine RSV have shown that RSV does not replicate in regional lymph nodes or palatine tonsils, although virus-positive cells can be found in the epithelial cells covering the pharyngeal tonsil [23]. At Day 4 post-infection, the infection spreads to the bronchiolar and alveolar epithelium, perhaps as a result of the cilia destruction of the bronchial epithelium.…”

“…At Day 4 post-infection, the infection spreads to the bronchiolar and alveolar epithelium, perhaps as a result of the cilia destruction of the bronchial epithelium. In the alveoli, RSV antigen can be detected in both type I and type II pneumocytes; however, type II pneumocytes are the main site of RSV replication [23]. Neutrophils seem to be the main phagocytizing cell of RSV antigens and particles that reach the bronchial lumen [23].…”

“…In the alveoli, RSV antigen can be detected in both type I and type II pneumocytes; however, type II pneumocytes are the main site of RSV replication [23]. Neutrophils seem to be the main phagocytizing cell of RSV antigens and particles that reach the bronchial lumen [23]. Alveolar macrophages (AM) are important in clearing neutrophils and debris [23].…”

“…Neutrophils seem to be the main phagocytizing cell of RSV antigens and particles that reach the bronchial lumen [23]. Alveolar macrophages (AM) are important in clearing neutrophils and debris [23]. It is believed that AM are non-migratory and do not contribute to the induction of adaptive immune responses; however, it has been shown that in mice, AM can migrate from the lung to the draining lymph node (dLN) and transport bacteria to this site, although their contribution to the induction of adaptive immune response in the dLN remains unknown [24].…”