Sarmento Luciana, Li Xia-qing, Howerth Elizabeth, Jackson Alan C, Fu Zhen F
Department of Pathology, University of Georgia, Athens, Georgia, USA.
J Neurovirol. 2005 Dec;11(6):571-81. doi: 10.1080/13550280500385310.
Induction of apoptosis by rabies virus (RV) has been reported to be associated with the expression of the glycoprotein (G), but inversely correlated with pathogenicity. To further delineate the association between the expression of the G and the induction of apoptosis, recombinant RVs with replacement of only the G gene were used to infect mice by the intracerebral route. Recombinant viruses expressing the G from attenuated viruses expressed higher level of the G and induced more apoptosis in mice than recombinant RV expressing the G from wild-type (wt) or pathogenic RV, demonstrating that it is the G gene that determines the level of G expression and, consequently, the induction of apoptosis. Likewise, recombinant viruses expressing the G from wt or pathogenic RV are more pathogenic in mice than those expressing G from attenuated RV, confirming the inverse correlation between RV pathogenicity and the induction of apoptosis. To investigate the mechanism by which induction of apoptosis attenuates viral pathogenicity, mice were infected with wt or attenuated RV by the intramuscular route. It was found that low doses of attenuated RV induced apoptosis in the spinal cord and failed to spread to the brain or produce neurological disease. On the other hand, apoptosis was not observed in the spinal cord of mice infected with the same doses of wt RV and the virus spread to various parts of the brain and induced fatal neurologic disease. These results suggest that glycoprotein-mediated induction of apoptosis limits the spread of attenuated rabies viruses in the central nervous system (CNS) of mice.
据报道，狂犬病病毒（RV）诱导的细胞凋亡与糖蛋白（G）的表达有关，但与致病性呈负相关。为了进一步阐明G的表达与细胞凋亡诱导之间的关联，仅替换G基因的重组RV通过脑内途径感染小鼠。与表达野生型（wt）或致病性RV的G的重组RV相比，表达减毒病毒G的重组病毒在小鼠中表达更高水平的G并诱导更多的细胞凋亡，这表明是G基因决定了G的表达水平，进而决定了细胞凋亡的诱导。同样，表达wt或致病性RV的G的重组病毒在小鼠中比表达减毒RV的G的重组病毒致病性更强，证实了RV致病性与细胞凋亡诱导之间的负相关。为了研究细胞凋亡诱导减弱病毒致病性的机制，通过肌肉途径用wt或减毒RV感染小鼠。发现低剂量的减毒RV在脊髓中诱导细胞凋亡，并且未能扩散到脑或引起神经疾病。另一方面，在感染相同剂量wt RV的小鼠脊髓中未观察到细胞凋亡，并且病毒扩散到脑的各个部位并引起致命的神经疾病。这些结果表明，糖蛋白介导的细胞凋亡诱导限制了减毒狂犬病病毒在小鼠中枢神经系统（CNS）中的传播。
