Recombinant rabies virus vaccine strain SAD-L16 inoculated intracerebrally in young mice produces a severe encephalitis with extensive neuronal apoptosis

Department of Microbiology and Immunology, Queen's University, Kingston, Ontario.
Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire (Impact Factor: 1.02). 05/2005; 69(2):100-5.
Source: PubMed


Seven-day-old ICR mice were infected by intracerebral inoculation with recombinant rabies virus vaccine strain SAD-L16. Infected mice developed severe and fatal encephalitis with rabies virus-infected neurons in widespread regions of the brain. There was extensive neuronal death with predominant features of apoptosis, as assessed by light and electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, and immunohistochemical staining for activated caspase-3. Although SAD-L16 is a neuroattenuated rabies virus, it is fully capable of spreading efficiently and inducing widespread neuronal apoptosis in the immature mouse brain.

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    • "Previously, SAD B19 strain of RV was mainly and successfully used as a seed for the construction of viral vectors for generating live vaccines for HIV/SIV, HCV or SARS-CoV (Faber et al., 2005b; Faul et al., 2009; McKenna et al., 2003; Siler et al., 2002) and delivering cytokines as chemokines, cytochrome C, TNF-␣ and IFN-␤ (Pulmanausahakul et al., 2001; Faber et al., 2005a; Faul et al., 2008; Zhao et al., 2009; Kuang et al., 2009). However, since even SAD B19 and its derivate SAD I16 were pathogenic when inoculated directly into mouse brains, further efforts to attenuate the virus are necessary (Vos et al., 1999; Mebatsion, 2001; Rasalingam et al., 2005). Therefore, in this report, the highly attenuated Chinese human RV vaccine strain CTN181 (Du et al., 2008) is recommended as a more suitable candidate seed strain for development of new viral vectors. "
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    • "The occurrence of neuronal death after encephalitis induced by rhabdoviruses remains controversial [41], [42], [43], [44], but in general, when it is unequivocally detected, it seems to be a microglial-mediated event (e.g. [45],[46]). "
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    • "96611) at a 1:200 dilution using a standard avidinbiotin complex ABC technique, as previously described (Rasalingam et al, 2005). Using the same methodology, we previously demonstrated specific caspase-3 immunostaining in many apoptotic brain neurons in an experimental model of rabies in mice (Rasalingam et al, 2005). Immunoperoxidase staining for the monocyte/macrophage marker CD68 (mouse monoclonal M0814, clone KP1, DAKO, at a 1:100 dilution) was also performed on selected serial sections of brain that showed positive staining for caspase-3. "
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