Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barré syndrome^1,2. While progress has been made in understanding the causal link between ZIKV infection and microcephaly^3-9, the life cycle and pathogenesis of ZIKV are less well understood. In particular, there are conflicting reports on the role of AXL, a TAM family kinase receptor that was initially described as the entry receptor for ZIKV^10-22. Here, we show that while genetic ablation of AXL protected primary human astrocytes and astrocytoma cell lines from ZIKV infection, AXL knockout did not block the entry of ZIKV. We found, instead, that the presence of AXL attenuated the ZIKV-induced activation of type I interferon (IFN) signalling genes, including several type I IFNs and IFN-stimulating genes. Knocking out type I IFN receptor α chain (IFNAR1) restored the vulnerability of AXL knockout astrocytes to ZIKV infection. Further experiments suggested that AXL regulates the expression of SOCS1, a known type I IFN signalling suppressor, in a STAT1/STAT2-dependent manner. Collectively, our results demonstrate that AXL is unlikely to function as an entry receptor for ZIKV and may instead promote ZIKV infection in human astrocytes by antagonizing type I IFN signalling.

中文翻译：

---

AXL通过拮抗I型干扰素信号传导促进星形胶质细胞中的寨卡病毒感染。

寨卡病毒（ZIKV）与新生儿小头畸形和格林巴里综合征^1,2有关。尽管在了解ZIKV感染与小头畸形^3-9之间的因果关系方面已取得进展，但对ZIKV的生命周期和发病机理的了解却很少。特别是，关于AXL的作用的报道相互矛盾，AXL是一种TAM家族激酶受体，最初被描述为ZIKV ^10-22的进入受体。在这里，我们显示，尽管AXL的基因消融保护了原代人星形胶质细胞和星形细胞瘤细胞系免受ZIKV感染，但AXL基因敲除并未阻止ZIKV的进入。相反，我们发现AXL的存在减弱了ZIKV诱导的I型干扰素（IFN）信号传导基因的激活，包括几种I型干扰素和IFN刺激基因。敲除I型IFN受体α链（IFNAR1）恢复了AXL敲除星形胶质细胞对ZIKV感染的脆弱性。进一步的实验表明，AXL以依赖于STAT1 / STAT2的方式调节SOCS1（一种已知的I型IFN信号抑制剂）的表达。总的来说，我们的结果表明，AXL不太可能充当ZIKV的进入受体，并可能通过拮抗I型IFN信号传导而促进人星形胶质细胞ZIKV感染。