Pathophysiology and clinical implications of lower respiratory tract infection (LRTI) with respiratory enteric orphan virus (reovirus): Background and experimental evidence.

摘要

Background. Respiratory viral infection early in life is a predominant factor in the inception of episodic wheezing and development of asthma amongst young children [1] and a serious health challenge. Previous studies of lower respiratory tract infections (LRTI) with respiratory syncytial virus (RSV) in animal models have indicated that early life viral exposure results in dysregulated neuroimmune interactions and altered synthesis/release of pro-inflammatory neuropeptides generating increased airway reactivity and neurogenic-inflammation. Similar to RSV, respiratory enteric orphan virus (Reovirus) is a common respiratory pathogen associated with pulmonary infections in children. Also, reovirus pulmonary infection has been shown to induce increased collagen deposition and be associated with the pathogenesis of bronchiolitis obliterans with organizing pneumonia (BOOP). In this study, we investigated the effects of reovirus exposure on physiological airway responses and whether these responses were associated with neurogenic inflammation and airway remodeling.;Methods. Adult (12 weeks) and weanling (2 weeks) Fisher-344 (F-344) rats were infected with reovirus or a pathogen-free vehicle and the changes in airway vascular permeability, neurotrophin expression, inflammatory response and protein content were measured at either 5 or 30 days after infection to determine changes in neurogenic inflammation and airway remodeling.;Results. Neurogenic inflammation increased in all treated animals 5 days after inoculation and up to 30 days in adult rats. This effect was not associated with any changes in nerve growth factor (NGF) and brain-derived neurotrphic factor (BDNF) expression in any animals at both time points. All treated animals developed acute pneumonia which resolved at 30 days. However, weanling rats showed mild peri-alveolar fibrosis at 30 days.;Conclusions. Reovirus potentiates neurogenic inflammation in rat airways. This effect is not associated with changes in neurotrophin expression. In weanling rats, reovirus infection induced peri-alveolar fibrosis suggesting that early exposure may carry long-term effects which may be clinically relevant.