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Updated: Aug 17, 2026
Mosaic Analysis of Gene Function in Postnatal Mouse Brain Development by Using Virus-based Cre Recombination
Published on: August 1, 2011
Screening of pro-apoptotic genes upregulated in an experimental street rabies virus-infected neonatal mouse brain
Sukathida Ubol1, Jitra Kasisith, Dhanesh Pitidhammabhorn
1Department of Microbiology, Faculty of Science, Mahidol University, Ratchatewee, Bangkok, Thailand. scsul@mahidol.ac.th
Abstract:
Rabies virus (RABV) is able to induce apoptotic death of target cells. The molecular pathway of RABV-induced cell death is partially known. In the present study, cDNA array analysis was used as a tool to screen for pro-apoptotic genes that may be involved in RABV induction. RNA was extracted from the infected CNS and from mock-infected controls. When the mean gene expression was compared between the infected group and controls, 21 potential apoptotic genes were identified that exhibited more than 2.5-fold difference in their expression levels. These 21 genes can be grouped into two groups, those genes that participate in the commitment phase and those that play a role as executioners. Examples of genes in commitment phase were death receptors (Fas-L receptor, TNF-receptor), lysosomal proteases, calpain, caspase-1, signaling molecules (ERK, p38MAPK) and bcl-2 family members. Cytochrome c and caspase-3 were representatives of executioners. Based on types of genes activated during the commitment phase, two independent apoptotic mechanisms may be activated in response to the RV infection. The first is immune-mediated death which may operate through the receptor-ligand pathway activated by caspase-1 and the pro-inflammatory cytokine, IL-1beta. The other mechanism is a protease-mediated process which involves lysosomal proteases and calcium-dependent neutral proteases. These two stimulating pathways were followed by Bad, Bak, Bid activation and subsequently the upregulation of cytochrome c and caspase-3. In addition, mobilization of K+ ion and other accessory apoptotic genes such as annexins and clusterin were also upregulated.
Insights
Rabies virus infection triggers programmed cell death (apoptosis) through two distinct pathways. This study identified 21 pro-apoptotic genes involved in rabies-induced apoptosis, offering new insights into viral pathogenesis.
Area of Science:
- * Molecular Biology
- * Virology
- * Immunology
Background:
- * Rabies virus (RABV) is known to induce apoptosis in host cells.
- * The precise molecular mechanisms underlying RABV-induced apoptosis are not fully understood.
Purpose of the Study:
- * To identify pro-apoptotic genes involved in RABV infection using cDNA array analysis.
- * To elucidate the molecular pathways of RABV-induced cell death.
Main Methods:
- * RNA extraction from infected and mock-infected central nervous system (CNS) tissues.
- * cDNA array analysis to compare gene expression profiles.
- * Identification of genes with >2.5-fold expression differences.
Main Results:
- * 21 pro-apoptotic genes were identified, categorized into commitment phase and executioner roles.
- * Commitment phase genes included death receptors, lysosomal proteases, caspases, and signaling molecules.
- * Executioner genes included cytochrome c and caspase-3, indicating activation of apoptotic pathways.
Conclusions:
- * RABV infection activates at least two independent apoptotic pathways: immune-mediated and protease-mediated.
- * These pathways involve receptor-ligand interactions, inflammatory cytokines, and protease cascades.
- * Upregulation of key apoptotic factors like cytochrome c and caspase-3 confirms cell death induction.
