Measles virus infection in a transgenic model: virus-induced immunosuppression and central nervous system disease.
Measles virus (MV) infects 40 million persons and kills one million per year primarily by suppressing the immune system and afflicting the central nervous system (CNS). The lack of a suitable small animal model has impeded progress of understanding how MV causes disease and the development of novel therapies and improved vaccines. We tested a transgenic mouse line in which expression of the MV receptor CD46 closely mimicked the location and amount of CD46 found in humans. Virus replicated in and was recovered from these animals' immune systems and was associated with suppression of humoral and cellular immune responses. Infectious virus was recovered from the CNS, replicated primarily in neurons, and spread to distal sites presumably by fast axonal transport. Thus, a small animal model is available for analysis of MV pathogenesis.
Oldstone
M B
MB
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA. mbaobo@scripps.edu
Lewicki
H
H
Thomas
D
D
Tishon
A
A
Dales
S
S
Patterson
J
J
Manchester
M
M
Homann
D
D
Naniche
D
D
Holz
A
A
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001921:Brain / Q000821:virology*; D002478:Cells, Cultured; D002494:Central Nervous System Infections / Q000473:pathology*; D018244:Chromosomes, Artificial, Yeast; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D007165:Immunosuppression Therapy; D008198:Lymph Nodes / Q000821:virology; D008214:Lymphocytes / Q000821:virology*; D008457:Measles / Q000821:virology*; D008459:Measles virus / Q000302:isolation & purification*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009474:Neurons / Q000821:virology; D013154:Spleen / Q000821:virology; D013997:Time Factors; D014018:Tissue Distribution
D015703:Antigens, CD; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins