A mouse model of persistent brain infection with recombinant Measles virus.
Measles virus (MV) nucleocapsids are present abundantly in brain cells of patients with subacute sclerosing panencephalitis (SSPE). This invariably lethal brain disease develops years after acute measles as result of a persistent MV infection. Various rodent models for MV infection of the central nervous system (CNS) have been described in the past, in which the detection of viral antigens is based on histological staining procedures of paraffin embedded brains. Here, the usage of a recombinant MV (MV-EGFP-CAMH) expressing the haemagglutinin (H) of the rodent-adapted MV-strain CAM/RB and the enhanced green fluorescent protein (EGFP) is described. In newborn rodents the virus infects neurons and causes an acute lethal encephalitis. From 2 weeks on, when the immune system of the genetically unmodified animal is maturating, intracerebral (i.c.) infection is overcome subclinically, however, a focal persistent infection in groups of neurons remains. The complete brain can be analysed in 50 or 100 microm slices, and infected autofluorescent cells are readily detected. Seven and 28 days post-infection (p.i.) 86 and 81% of mice are infected, respectively, and virus persists for more than 50 days p.i. Intraperitoneal immunization with MV 1 week before infection, but not after infection, protects and prevents persistence. The high percentage of persistence demonstrates that this is a reliable and useful model of a persistent CNS infection in fully immunocompetent mice, which allows the investigation of determinants of the immune system.
Schubert
S
S
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Straße 7, D-97078 Würzburg, Germany.
Möller-Ehrlich
K
K
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Straße 7, D-97078 Würzburg, Germany.
Singethan
K
K
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Straße 7, D-97078 Würzburg, Germany.
Wiese
S
S
Institute for Clinical Neurobiology, University of Würzburg, D-97078 Würzburg, Germany.
Duprex
W P
WP
School of Biomedical Sciences, The Queen's University of Belfast, Belfast BT9 7BL, UK.
Rima
B K
BK
School of Biomedical Sciences, The Queen's University of Belfast, Belfast BT9 7BL, UK.
Niewiesk
S
S
College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210-1093, USA.
Schneider-Schaulies
J
J
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Straße 7, D-97078 Würzburg, Germany.
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D006389:Hemagglutinins, Viral / Q000235:genetics; D006801:Humans; D007114:Immunization; D007121:Immunocompetence; D008457:Measles / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000821:virology; D008459:Measles virus / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000821:virology; D011994:Recombinant Proteins / Q000235:genetics; D011995:Recombination, Genetic; D013344:Subacute Sclerosing Panencephalitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000473:pathology
D006389:Hemagglutinins, Viral; D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins