Respiratory syncytial virus: the virus, the disease and the immune response

Abstract

RSV is the primary cause of hospitalisation in the first year of life for children in most parts of the world, and nearly 100% of children in the USA are infected with the virus by 2 to 3 years of age. The agent is an enveloped RNA virus with a non-segmented single-stranded negative-sense genome. The viral genome encodes 8 structural and 2 non-structural proteins. Important structural proteins include the fusion (F) protein and the attachment (G) protein which are essential for viral penetration and attachment to the host cells. Both proteins are important in development of immune responses. The virus is estimated to cause 3000 to 4000 deaths annually. Primary infections are as a rule symptomatic. The spectrum of clinical manifestations ranges from mild upper tract illness, infection in middle ear which progresses to acute otitis media, croup, to apnoea in premature infants, pneumonia and bronchiolitis. Premature babies born at 30-35 weeks of gestation, infants with cyanotic congenital heart disease, HIV-infected subjects, and patients on intensive immunosuppressive therapy especially after bone marrow transplant are considered to be at risk for increased mortality and morbidity during RSV infection. The virus does not normally replicate outside of the bronchopulmonary tree and the infection is exquisitely restricted to the respiratory mucosa. However, development of extrapulmonary disease has been observed in certain T and B cell immunodeficiency states. The association of RSV with asthma and reversible reactive airway disease in early childhood has attracted significant attention. Recurrent wheezing for up to 5 to 7 years of age and established airway disease has been observed in a significant number of children with a strong family history of allergy, after primary infection or reinfection with RSV. Immune response to primary infection is relatively small but on reinfection, a significant booster effect with sustained immunologic reactivity is observed in serum and respiratory mucosa. Both CD(4)- and CD(8)-specific as well as Th(1)- and Th(2)-cell specific immune responses have been observed during human infection. In addition, proinflammatory as well as immunoregulatory cytokines and chemokines are induced in the respiratory tract after natural and induced (in vitro) infection. Significant progress has been made in understanding the role of Th(1) vs. Th(2), IgE, viral induced cytokines and chemokines in the mechanisms of pathogenesis of the disease, development of wheezing and in the prevention and treatment of the infection and its sequelae. Respiratory syncytial virus (RSV) is one of the commonest human viral infections, and virtually every child is infected by the third birthday. Because of its restricted mucosal immunopathology, and frequent association with bronchial hyperreactivity and development of wheezing, RSV has served as an important model to investigate mechanisms of mucosal immune responses and development of mucosal disease following infection. The importance of RSV in bronchopulmonary disease and development of bronchial hyperreactivity has been the focus of several recent symposia [Kimpen JL, Simoes EAF. Am J Respir Crit Care Med 2001; 163:S1-S6]. This brief report will only summarise, based on selected references, the historical landmarks of its discovery and current understanding of the mechanisms of immunity, and their possible role in the pathogenesis of bronchopulmonary disease.