Respiratory Syncytial Virus

Human respiratory syncytial virus (hRSV) is the leading cause of acute lower respiratory infections in infants and young children worldwide. Epithelial cells lining the nasal passages and respiratory tract are the primary target of hRSV infection. Replication of hRSV in the host cell follows the general strategy of the Mononegavirales. Cells respond to hRSV infection by producing a variety of cytokines, chemokines and interferons that are involved in the host inflammatory response. Although primary hRSV infection occurs at an early age, immunity is short-lived or incomplete and reinfections occur throughout life. In fact, hRSV is also a pathogen of major importance for the elderly and immunocompromised adults. Initial efforts to develop a vaccine based on formalin-inactivated virus resulted in vaccine-enhanced disease after natural infection. However, recent advances on hRSV immunobiology have brought effective vaccines and antivirals as realistic objectives in a foreseeable future. Key Concepts Human respiratory syncytial virus (hRSV) is the leading cause of serious respiratory tract disease in children and infants worldwide but also a pathogen of recognised importance in the elderly and immunocompromised adults. hRSV belongs to the Orthopneumovirus genus of the Pneumoviridae family within the Mononegavirales order 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. 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 the hRSV fusion protein, is the only product available in the market for specific prophylactic treatment of children at high risk of severe infection.