Infection of SCID mice with Montana Myotis leukoencephalitis virus as a model for flavivirus encephalitis.
We have established a convenient animal model for flavivirus encephalitis using Montana Myotis leukoencephalitis virus (MMLV), a bat flavivirus. This virus has the same genomic organization, and contains the same conserved motifs in genes that encode potential antiviral targets, as flaviviruses that cause disease in man (N. Charlier et al., accompanying paper), and has a similar particle size (approximately 40 nm). MMLV replicates well in Vero cells and appears to be equally as sensitive as yellow fever virus and dengue fever virus to a selection of experimental antiviral agents. Cells infected with MMLV show dilation of the endoplasmic reticulum, a characteristic of flavivirus infection. Intraperitoneal, intranasal or direct intracerebral inoculation of SCID mice with MMLV resulted in encephalitis ultimately leading to death, whereas immunocompetent mice were refractory to either intranasal or intraperitoneal infection with MMLV. Viral RNA and/or antigens were detected in the brain and serum of MMLV-infected SCID mice, but not in any other organ examined: MMLV was detected in the olfactory lobes, the cerebral cortex, the limbic structures, the midbrain, cerebellum and medulla oblongata. Infection was confined to neurons. Treatment with the interferon-alpha/beta inducer poly(I).poly(C) protected SCID mice against MMLV-induced morbidity and mortality, and this protection correlated with a reduction in infectious virus titre and viral RNA load. This validates the MMLV model for use in antiviral drug studies. The MMLV SCID model may, therefore, be attractive for the study of chemoprophylactic or chemotherapeutic strategies against flavivirus infections causing encephalitis.
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium1.
Nathalie
N
Charlier
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium1.
Pieter
P
Leyssen
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium1.
Jan
J
Paeshuyse
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany2.
Christian
C
Drosten
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany2.
Herbert
H
Schmitz
Division of Histopathology, University Hospitals, B-3000 Leuven, Belgium3.
Alfons
A
Van Lommel
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium1.
Erik
E
De Clercq
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium1.
Johan
J
Neyts
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology / Q000821:virology; D005416:Flavivirus / Q000187:drug effects / Q000472:pathogenicity*; D018177:Flavivirus Infections / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology / Q000821:virology; D007962:Leukocytes / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D012367:RNA, Viral / Q000097:blood; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D012367:RNA, Viral