Respiratory syncytial virus (RSV) is the leading cause for childhood hospitalization and respiratory distress, being recognized as a major health and economic burden worldwide. RSV can exploit host immunity and cause a strong inflammatory response that leads to lung damage and virus dissemination. Unfortunately, the immune response elicited by RSV normally fails to protect against subsequent exposures to the virus. Despite intense research during the 50 years after the discovery of RSV, scientists are just beginning to understand the mechanisms contributing to pathology and to the inadequate immune response shown by susceptible individuals. Here, we discuss some of the most important advances made in this field that could lead to the development of new prophylactic tools.
INTRODUCTIONRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children in the world, as well of infant hospitalization due to respiratory disease. In the USA alone, RSV causes approximately 125 000 annual hospitalizations [1]. Because of the high infectivity of the virus, nearly 70% of children are infected by the age of 1 year, whereas almost 100% have been exposed to the virus during their second year of life. Importantly, about 36% of infants under 2 years have suffered at least two infections [2,3]. Although infection rates for RSV are similar throughout the world, severe pathology predominantly occurs in infants displaying risk factors, such as incomplete airway development due to premature birth, pulmonary hypertension, airway hyper-reactivity, congenital heart disease and immunosuppression [4]. Furthermore, RSV-associated acute lower respiratory infection and RSV-associated fatality ratios are higher in infants residing in developing countries [5].Respiratory syncytial virus belongs to the Paramyxoviridae family, which also includes measles, parainfluenza 3, Hendra and Nipah viruses. Together with the recently identified human metapneumovirus, RSV is more specifically classified into the subfamily Pneumovirinae [6]. RSV is an enveloped virus with 10 genes distributed along 15.2 kilobases of negative-stranded RNA that encode 11 proteins (Figure 1). Eight of the RSV proteins are known to be structural and so present in the virion particle (Figure 1). The two non-structural proteins, NS1 and NS2, are expressed only during cell infection and are not packaged into the virion. Whether the M2 gene product, M2-2, is packaged within the virion remains to be determined. Despite extensive research efforts, no vaccines are currently available that are capable of inducing long-lasting protective immunity against this virus. Nevertheless, although a widely used prophylactic strategy based on a humanized neutralizing antibody has been shown to be effective at preventing RSV-induced damage, its high cost has limited the use of this treatment only for high-risk groups, such as preterm infants (<37 weeks of gestational age) and infants suffering from cardiovascular diseases and immunosuppress...