Human Respiratory Syncytial Virus
Peter L. Collins
from: The Biology of Paramyxoviruses (Edited by: Siba K. Samal). Caister Academic Press, U.K. (2011)
Human respiratory syncytial virus (RSV) is a ubiquitous pathogen that infects essentially everyone worldwide during infancy and early childhood and is a leading cause of pediatric hospitalization for respiratory disease. RSV also is a frequent cause of less severe disease in healthy adults and is an important cause of morbidity and mortality in the elderly and in severely immunosuppressed individuals. RSV is an enveloped nonsegmented negative strand RNA virus classified in the Paramyxoviridae family, and its genome organization is one of the more complex of this family. The genome includes: two separate genes encoding type I and type III interferon (IFN) antagonists (NS1 and NS2); a gene (M2) with two open reading frames encoding novel proteins (M2-1 and M2-2) involved in RNA synthesis; and an attachment protein G that has a number of unusual features, including high sequence variability, heavy glycosylation, cytokine mimicry, and a shed form that helps the virus evade neutralizing antibodies. RSV is able to efficiently infect and cause disease in very young infants, with the peak of hospitalization at 2-3 months of age, despite the presence of maternally derived virus-neutralizing serum antibodies. RSV has a single serotype but is able to re-infect symptomatically throughout life without the need for significant antigenic change, although immunity from prior infection reduces disease. It is widely thought that re-infection is due to an ability of RSV to inhibit or subvert the host immune response, but this remains largely speculative. The development of an effective vaccine or specific antiviral therapy against RSV is considered a high priority, but these goals remain unfulfilled. RSV is notable for a historic vaccine failure: a formalin-inactivated RSV vaccine that was evaluated in infants and children in the 1960's was poorly protective and paradoxically primed for enhanced RSV disease upon subsequent natural RSV infection. However, RSV also is notable because of the development of a successful strategy for passive immunoprophylaxis of infants at high risk for serious RSV disease using an RSV-neutralizing monoclonal antibody (MAb) read more ...