Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.
Trends Pharmacol Sci. 2011 Jan;32(1):2-7. doi: 10.1016/j.tips.2010.11.001. Epub 2010 Dec 7.
Although coronavirus tropism is most often ascribed to receptor availability, increasing evidence suggests that for the neurotropic strains of the murine coronavirus mouse hepatitis virus (MHV), spike-receptor interactions cannot fully explain neurovirulence. The canonical MHV receptor CEACAM1a and its spike-binding site have been extensively characterized. However, CEACAM1a is poorly expressed in neurons, and the extremely neurotropic MHV strain JHM.SD infects ceacam1a(-/-) mice and spreads among ceacam1a(-/-) neurons. Two proposed alternative MHV receptors, CEACAM2 and PSG16, also fail to account for neuronal spread of JHM.SD in the absence of CEACAM1a. It has been reported that JHM.SD has an unusually labile spike protein, enabling it to perform receptor-independent spread (RIS), but it is not clear if the ability to perform RIS is fully responsible for the extremely neurovirulent phenotype. We propose that the extreme neurovirulence of JHM.SD is multifactorial and might include as yet unidentified neuron-specific spread mechanisms.
尽管冠状病毒的嗜性通常归因于受体的可用性，但越来越多的证据表明，对于神经嗜性的鼠冠状病毒鼠肝炎病毒 (MHV) 株，刺突-受体相互作用不能完全解释其神经毒力。经典的 MHV 受体 CEACAM1a 及其刺突结合位点已得到广泛研究。然而，CEACAM1a 在神经元中的表达水平较低，而极度神经嗜性的 MHV 株 JHM.SD 可感染 ceacam1a(-/-) 小鼠并在 ceacam1a(-/-)神经元中传播。另外两个被提出的 MHV 受体 CEACAM2 和 PSG16，在缺乏 CEACAM1a 的情况下，也不能解释 JHM.SD 向神经元的传播。据报道，JHM.SD 的刺突蛋白异常不稳定，使其能够进行受体非依赖性传播（RIS），但尚不清楚是否具有 RIS 能力完全是其极度神经毒力表型的原因。我们提出，JHM.SD 的极度神经毒力是多因素的，可能包括尚未确定的神经元特异性传播机制。
