Inflammation and Therapy for Respiratory Virus Infection

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This year, together with collaborators at SUNY Upstate Medical University, New York and University of Newcastle, Australia, I have contributed to two original reports describing translational advances. In the first of these studies, we examined the inflammatory responses of older, but otherwise immunologically naive mice to infection with pneumonia virus of mice (PVM). Although we see no changes in the extent or kinetics of virus replication, we observe diminished local production of inflammatory mediators. Age-dependent diminished production of proinflammatory mediators was associated with diminished recruitment of granulocytes and reduced severity of clinical responses, including weight loss and respiratory dysfunction. The differences observed when comparing these results to those reported among elderly human subjects may be related to the specific extent of aging and its impact on biochemical and cellular inflammatory responses and/or the role of lifetime virus re-exposure on the clinical outcome from acute pneumovirus disease (Bonville et al. Virology 2007). In a second study, we explored the possibility that eosinophils play a direct role in promoting clearance of the prevalent respiratory pathogen, respiratory syncytial virus (RSV) when used in an intranasal challenge model in mice. Specifically, we found that virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice than in wild type mice. In terms of mechanism, we demonstrated that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after ssRNA stimulation of the TLR7-MyD88 pathway. Collectively, the results demonstrate that eosinophils promote virus clearance and may thus limit virus-induced lung dysfunction. (Phipps et al. Blood 2007). I have also published an invited, peer-reviewed manuscript describing the pneumonia virus of mice model entitled "Pneumonia virus or mice: severe respiratory virus infection in a natural host" (Immunol Lett 2008; 118: 6 - 12)