Respiratory Syncytial Virus

Abstract

Human respiratory syncytial virus (HRSV) is a ubiquitous ribonucleic acid (RNA) virus that represents the leading cause of acute lower respiratory infections (mainly bronchiolitis and pneumonia) in infants and young children worldwide. HRSV belongs to the Pneumovirinae subfamily within the Paramyxoviridae family of enveloped, negative‐strand RNA viruses. Epithelial cells lining the nasal passages and respiratory tract are the primary target of HRSV infection, although alveolar macrophages and dendritic cells are also infected. Infected cells respond by producing a variety of cytokines, chemokines and interferons that are involved in the inflammatory response to HRSV. Although primary HRSV infection occurs at an early age, immunity is short‐lived or incomplete and re‐infections occur throughout life. Initial efforts to develop a vaccine based on formalin‐inactivated HRSV resulted in vaccine‐enhanced disease, and there is still no licensed prophylactic HRSV vaccine available. Key Concepts: Human respiratory syncytial virus (HRSV) is the leading cause of serious respiratory tract disease in children and infants worldwide. HRSV belongs to the Pneumovirinae subfamily within the Paramyxoviridae family of negative‐strand RNA viruses. The HRSV genome comprises 10 genes that encode 11 viral proteins. HRSV derives its name from the formation of multinucleated, fused cells (syncytia), which are the hallmark of infection of cultured cells or lung tissue. Following attachment to the target cell, entry by HRSV is mediated by fusion of the viral envelope with the host cell plasma membrane at neutral pH. The entire replication cycle of HRSV takes place in the cytoplasm of the infected cell. Reverse genetics has permitted the recovery of infectious HRSV from complementary DNA. HRSV strains disseminate rapidly worldwide, accumulating mutations predominantly in the attachment protein, probably as a consequence of immune selection. Pathology associated with HRSV infections is not only the result of direct virus injury, but largely the consequence of an aberrant immune/inflammatory response. Palivizumab, a neutralising monoclonal antibody directed against HRSV fusion protein, is the only product available on the market for prophylactic treatment of children at high risk of severe infection.