RESUMEN
UNLABELLED: Among the factors influencing airway function are neural control mechanisms, including adrenergic, cholinergic, nonadrenergic noncholinergic inhibitory, and nonadrenergic noncholinergic excitatory pathways. Respiratory infections affect these pathways in ways that are not entirely clear. OBJECTIVE: To determine acute and chronic effects of respiratory syncytial virus infection on airway neural control mechanisms. STUDY DESIGN: Acute effects were studied in cotton rats, which received human respiratory syncytial virus or uninfected cell culture medium intranasally at 5 weeks of age. Chronic effects were studied in ferrets, which received human respiratory syncytial virus or uninfected cell culture medium intranasally during the first 10 days of life. The responsiveness of tracheal smooth muscle segments was studied in vitro 4 days after infection of cotton rats and when ferrets were 4, 8, and 24 weeks of age. RESULTS: Tracheal smooth muscle segments from cotton rats demonstrated significant increases in contractile responses to nerve stimulation (cholinergic responses). In the presence of neurokinin A, contractile responses increased (enhanced nonadrenergic noncholinergic excitatory response), and relaxation of airways by nerve stimulation (nonadrenergic noncholinergic inhibitory response) was severely impaired. Airway epithelium was also disrupted. These alterations favor airway obstruction and a hyper-responsive state. Contractile responses to nerve stimulation were increased in 4- and 8-week-old ferrets infected with human respiratory syncytial virus compared with ferrets in a control group, a difference that resolved by 24 weeks. Nonadrenergic noncholinergic inhibitory responses were absent in all 4-week-old ferrets and significantly decreased in 8-week-old ferrets infected with human respiratory syncytial virus. A significant difference persisted at 24 weeks of age. CONCLUSION: Human respiratory syncytial virus causes acute and chronic changes in neural control of airways in animal models. When infection occurs early in life, the alterations persist for long periods.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio/fisiopatología , Tráquea/fisiopatología , Tráquea/virología , Enfermedad Aguda , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Hurones , Humanos , Contracción Muscular , Músculo Liso/fisiopatología , Músculo Liso/virología , Ratas , Infecciones por Virus Sincitial Respiratorio/patología , SigmodontinaeRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) has been associated with nasopharyngeal carcinoma, some lymphomas, and lymphoproliferative disease after organ transplantation. Many lymphoproliferative tumors that occur after transplantation are clonal, a property that classifies them as neoplastic. Clonality can be determined by analysis of the extrachromosomal circular DNA episomes produced by EBV infection. METHODS: We describe three young children in whom smooth-muscle tumors developed 18 months to 5 1/2 years after liver transplantation with immunosuppression. We examined the tumors by microscopy and with immunohistochemical studies and molecular genetic analyses of the EBV DNA: RESULTS: The tumors were composed of spindle cells with smooth-muscle features and resembled those described in patients with the acquired immunodeficiency syndrome. Immunohistochemical analysis was negative for EBV latent membrane protein and EBV receptor (CD21), but positive for EBV nuclear antigen 2. In situ hybridization revealed nuclear EBV sequences, and molecular genetic analysis showed the EBV genome to be clonal in all three patients. CONCLUSIONS: Smooth-muscle tumors that developed after organ transplantation contained clonal EBV, suggesting that the virus has a role in the development of these neoplastic lesions.