Studies on the natural course of RSV-, HMPV, and RSV/HMPV- double-infections in children in an optimized animal model

Human metapneumovirus and human respiratory syncytial virus cause mild to severe infections of the respiratory tract in all age groups. It was hypothesized that HMPV infection are generally milder than RSV infections, but meanwhile it turned out that this is not true in hospitalized patients. However, despite distinct genetically differences between both viruses it so far remains unclear how far both viruses induce different innate immune responses and clinical patterns in otherwise healthy individuals and how far they influence each other in double infections, a condition frequently observed in clinical settings. Here, it is demonstrated that both RSV and HMPV induce milder disease in mice than hitherto assumed. Thereby, much of virus specific effects published so far can be deduced to technical problems during infection experiments that we solved in an optimized infection model that better emulates the natural course of infection. Furthermore we show that HMPV infections tend to induce a more severe infection that can be deduced to a different cell autonomous immunity. The present study gives raise to the assumption that experimental and technical conditions in HMPV, RSV, and maybe further studies investigating on respiratory viruses need to be optimized. Key-Words: HMPV; RSV; coinfection