Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis

Abstract

Human respiratory syncytial virus (RSV) was first isolated in 1956 from a laboratory chimpanzee with upper respiratory tract disease (for general reviews, see references 21, 57, 102, and 145).RSV was quickly determined to be of human origin and was shown to be the leading worldwide viral agent of serious pediatric respiratory tract disease.In a 13-year prospective study of infants and children in the United States, RSV was detected in 43%, 25%, 11%, and 10% of pediatric hospitalizations for bronchiolitis, pneumonia, bronchitis, and croup, respectively (110).Approximately two-thirds of infants are infected with RSV during the first year of life, and 90% have been infected one or more times by 2 years of age.The rate of hospitalization for primary infection is approximately 0.5% but can vary by situation and ethnic group and can be as high as 25% (77).RSV also is a significant cause of morbidity and mortality in the elderly, with an impact approaching that of nonpandemic influenza virus (39).RSV readily infects severely immunocompromised individuals, most notably allogeneic bone marrow transplant recipients, causing high mortality.RSV also makes a substantial contribution to upper respiratory tract disease in individuals of all ages (59, 65).Globally, the World Health Organization estimates that RSV causes 64 million infections and 160,000 deaths annually (Initiative for Vaccine Research: respiratory syncytial virus, World Health Organization [http: //www.who.int/vaccine_research/diseases/ari/en/index3.html,accessed 5 December 2005]).Although RSV has a single serotype, reinfection can occur throughout life.RSV in yearly winter/early spring epidemics in temperate regions; elsewhere, the timing of RSV activity can vary widely with the locale.The RSV reservoir in the offseason is unknown.Strains circulate quickly around the earth (150).Neither a vaccine nor an effective antiviral therapy is available, although there is active research in both areas (23,78, 138).However, infants at high risk for serious disease can receive passive immunoprophylaxis during the epidemic season by a monthly injection of a commercial RSV-neutralizing monoclonal antibody, palivizumab (Synagis), which provides a 55% reduction in RSV-associated hospitalization (17).