Lymphatic dissemination and comparative pathology of recombinant measles viruses in genetically modified mice

The dissemination of the Edmonston measles virus (Ed-MV) vaccine strain was studied with genetically modified mice defective for the alpha/beta interf eron receptor and expressing human CD 16 with human-like tissue specificity and efficiency. A few days after intranasal infection, macrophages express ing Ed-MV RNA were detected in the lungs, in draining lymph nodes, and in t he thymus. In lymph nodes, large syncytia which stained positive for viral RNA and for macrophage surface marker proteins were found and apoptotic cel l death was monitored. In the thymus, smaller syncytia which stained positi ve for macrophage and dendritic cell markers were detected,Thus, macrophage s appear to be the main vectors for dissemination of MV infection in these mice: human macrophages may have a similar function in the natural host. We then compared the pathogenicities of two recombinant viruses lacking the C of V nonstructural proteins to that of the parental strain, Ed-MV. These v iruses were less effective in spreading through the lymphatic system and, u nlike Ed-MV were not detected in the liver, After intracerebral inoculation the recombinant viruses caused lethal disease less often than Ed-MV and in duced distinctive patterns of gliosis and inflammation. Ed-MV was reisolate d from brain tissue, but its derivatives were not. C- and V-defective virus es should be considered as more-attenuated MV vaccine candidates.