Abstract：
Rabies, caused by lyssavirus rabies (Rabies lyssavirus, RABV), is a fatal disease among humans and almost all warm-blooded animals. In this study, we found that RABV infection induces the up-regulation of receptor transporter protein 4 (RTP4) in mouse brains and different cells of nervous tissue. Over-expression of RTP4 reduces the viral titer of RABV in different neuronal cells. Furthermore, a recombinant RABV expressing RTP4, named rRABV-RTP4, was constructed and displayed a lower viral titer in different neuronal cells due to the expression of RTP4. Moreover, the survival rates of mice infected with rRABV-RTP4 were significantly higher than those of mice infected with parent virus rRABV or control virus rRABV-RTP4(-). In terms of mechanism, RTP4 could bind viral genomic RNA (vRNA) of RABV, and suppress the whole viral genome amplification. In addition, we found that the zinc finger domain (ZFD) of RTP4 exerts the antiviral function by truncation analysis, and an important amino acids site (C95) in the RTP4 3CxxC motif which is essential for its antiviral function was identified by mutation analysis. This study contributes to our understanding of how RTP4 or other RTP proteins play a role in defense against the invasion of RABV or other viruses.
摘要：
狂犬病,由狂犬病病毒引起的(狂犬病病毒，RABV),是人类和几乎所有温血动物的致命疾病。在这项研究中,我们发现RABV感染诱导小鼠大脑和神经组织不同细胞中受体转运蛋白4（RTP4）的上调。RTP4的过表达降低了不同神经元细胞中RABV的病毒滴度。此外，构建了表达RTP4的重组RABV，称为rRABV-RTP4，由于RTP4的表达，在不同的神经元细胞中显示较低的病毒滴度。此外，感染rRABV-RTP4的小鼠的存活率明显高于感染亲本病毒rRABV或对照病毒rRABV-RTP4的小鼠(-)。在机制方面,RTP4可以结合RABV的病毒基因组RNA（vRNA），并抑制整个病毒基因组的扩增。此外,我们发现RTP4的锌指结构域（ZFD）通过截短分析发挥抗病毒功能，并且通过突变分析鉴定了RTP43CxxC基序中对其抗病毒功能至关重要的重要氨基酸位点（C95）。这项研究有助于我们了解RTP4或其他RTP蛋白如何在防御RABV或其他病毒入侵中发挥作用。
