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 interferon receptor and expressing human CD46 with human-like tissue specificity and efficiency. A few days after intranasal infection, macrophages expressing Ed-MV RNA were detected in the lungs, in draining lymph nodes, and in the thymus. In lymph nodes, large syncytia which stained positive for viral RNA and for macrophage surface marker proteins were found and apoptotic cell death was monitored. In the thymus, smaller syncytia which stained positive for macrophage and dendritic cell markers were detected. Thus, macrophages 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 or V nonstructural proteins to that of the parental strain, Ed-MV. These viruses were less effective in spreading through the lymphatic system and, unlike Ed-MV, were not detected in the liver. After intracerebral inoculation the recombinant viruses caused lethal disease less often than Ed-MV and induced distinctive patterns of gliosis and inflammation. Ed-MV was reisolated from brain tissue, but its derivatives were not. C- and V-defective viruses should be considered as more-attenuated MV vaccine candidates.
Mrkic
B
B
Molecular Biology Institute, University of Zurich, Switzerland.
Odermatt
B
B
Klein
M A
MA
Billeter
M A
MA
Pavlovic
J
J
Cattaneo
R
R
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D001921:Brain / Q000473:pathology; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology*; D015726:Giant Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology / Q000821:virology; D008168:Lung / Q000473:pathology / Q000821:virology; D008208:Lymphatic System / Q000473:pathology / Q000821:virology*; D008264:Macrophages / Q000821:virology; D008457:Measles / Q000473:pathology* / Q000821:virology; D008459:Measles virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D017471:Receptors, Interferon / Q000032:analysis / Q000235:genetics; D014779:Virus Replication
D015703:Antigens, CD; C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D017471:Receptors, Interferon