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Updated: May 3, 2026
Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome
Published on: June 10, 2013
Mutant murine hepatitis virus-induced apoptosis in the hippocampus
Masatoshi Kakizaki1, Hiromi Kashiwazaki, Rihito Watanabe
1Department of Bioinformatics, Faculty of Engineering, Soka University.
Abstract:
The mutant virus Mu-3 was isolated from the soluble receptor-resistant mutant 7 virus (srr7), which is a neuropathogenic strain of the mouse hepatitis virus JHMV, and cloned as a soluble receptor-resistant mutant from the highly neuropathogenic JHMV strain cl-2 virus (cl-2). In order to identify specific characteristics of Mu-3, the pathology of Mu-3-infected mice was compared with that of srr7- and cl-2-infected mice. The neuropathology after Mu-3 infection exhibited a mixed pattern comparable to that induced by srr7 and cl-2 infections. In addition, Mu-3 infection caused marked apoptotic lesions in the hippocampal region, particularly in the CA2 and CA3 subregions, in the brains of all infected mice. In contrast, in cl-2 infection, 10-20% of the infected mice exhibited apoptosis in the hippocampus, which was primarily observed in the CA1 subregion. Apoptosis also occurred in the pyramidal neurons and CD11b-bearing cells. The apoptotic cells, indicated by caspase 3-activation, were a mixed population of infected and a higher number of uninfected cells. These data indicated that apoptosis observed in Mu-3 infection could be induced by the indirect effects of infection in addition to direct effects of the infected cells occurring in a cell-autonomous manner.
Insights
The novel mouse hepatitis virus Mu-3 causes significant brain apoptosis in mice, affecting both infected and uninfected cells. This suggests indirect infection effects contribute to neuropathology.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Mouse hepatitis virus (JHMV) is a neuropathogenic strain.
- Soluble receptor-resistant mutants (srr7 and cl-2) are derived from JHMV.
- Mu-3 is a novel mutant derived from srr7 and cl-2.
Purpose of the Study:
- To characterize the neuropathology of the Mu-3 JHMV strain.
- To compare Mu-3 infection with srr7 and cl-2 infections in mice.
- To investigate the mechanisms of apoptosis induced by Mu-3.
Main Methods:
- Infection of mice with Mu-3, srr7, and cl-2 strains.
- Comparative neuropathological analysis of infected mouse brains.
- Identification of apoptotic cells using caspase 3 activation.
Main Results:
- Mu-3 infection induced a mixed neuropathological pattern similar to srr7 and cl-2.
- Mu-3 caused widespread apoptotic lesions in the hippocampus (CA2, CA3 regions).
- Apoptosis involved both infected and uninfected cells, suggesting indirect effects.
Conclusions:
- Mu-3 exhibits distinct neuropathogenic properties, inducing significant hippocampal apoptosis.
- Apoptosis in Mu-3 infection results from both direct and indirect effects.
- Understanding Mu-3 pathogenesis provides insights into JHMV-induced neurological disease.
