Kuang Yi, Lackay Sarah N, Zhao Ling, Fu Zhen F
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Virus Res. 2009 Sep;144(1-2):18-26. doi: 10.1016/j.virusres.2009.03.014. Epub 2009 Apr 5.
Induction of innate immunity, particularly through the induction of interferon and chemokines, by rabies virus (RABV) infection has been reported to be inversely correlated with pathogenicity. To further investigate the association between the expression of chemokines and RABV infection, laboratory-attenuated RABV (B2C) and wild-type (wt) RABV (DRV) were administered to Balb/c mice intramuscularly. Chemokine expression, inflammatory cell infiltration, and blood-brain barrier (BBB) permeability were evaluated at various time points after infection. At day 3 post-infection (p.i.) there was very little inflammation in the central nervous system (CNS) and BBB permeability did not change in mice infected with either virus when compared with mock-infected mice. At 6 day p.i., infection with B2C induced the expression of inflammatory chemokines and infiltration of inflammatory cells into the CNS, while these changes were minimal in DRV-infected mice. Furthermore, infection with B2C significantly enhanced BBB permeability comparing to infection with DRV. Among the upregulated chemokines, the expression of IP-10 was best correlated with infiltration of inflammatory cells into the CNS and enhancement of BBB permeability. These data indicate that laboratory-attenuated RABV induces expression of chemokines and infiltration of inflammatory cells into the CNS. Upregulation of chemokines by B2C may have triggered the change in BBB permeability, which helps infiltration of inflammatory cells into the CNS, and thus attenuation of RABV.
据报道，狂犬病病毒（RABV）感染诱导固有免疫，特别是通过诱导干扰素和趋化因子，这与致病性呈负相关。为了进一步研究趋化因子表达与RABV感染之间的关联，将实验室减毒的RABV（B2C）和野生型（wt）RABV（DRV）肌肉注射给Balb/c小鼠。在感染后的不同时间点评估趋化因子表达、炎性细胞浸润和血脑屏障（BBB）通透性。感染后第3天（p.i.），中枢神经系统（CNS）炎症非常轻微，与 mock 感染小鼠相比，感染两种病毒的小鼠的BBB通透性均未改变。感染后第6天，B2C感染诱导炎性趋化因子表达以及炎性细胞浸润到CNS中，而在DRV感染的小鼠中这些变化最小。此外，与DRV感染相比，B2C感染显著增强了BBB通透性。在上调的趋化因子中，IP-10的表达与炎性细胞浸润到CNS中以及BBB通透性增强的相关性最好。这些数据表明，实验室减毒的RABV诱导趋化因子表达以及炎性细胞浸润到CNS中。B2C引起的趋化因子上调可能触发了BBB通透性的变化，这有助于炎性细胞浸润到CNS中，从而导致RABV减毒。
