Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

寨卡病毒 (ZIKV) 具有穿越胎盘和脑屏障的能力，可导致新生儿先天畸形和成人神经系统疾病。然而，ZIKV 诱导成人神经系统并发症和先天性畸形的发病机制仍未完全了解。Gas6 是一种可溶性 TAM 受体配体，能够促进黄病毒内化和免疫反应的下调。在这里，我们证明了具有较高 Gas6 水平的 ZIKV 神经系统并发症与与抗病毒反应相关的基因下调之间存在相关性，如Socs1引起的 I 型干扰素上调。此外，Gas6 γ-羧化对于 ZIKV 在单核细胞中的侵袭和复制是必不可少的，单核细胞是这种蛋白质的主要来源，被华法林抑制。相反，Gas6 促进成年免疫活性小鼠中的 ZIKV 复制，并使对经胎盘感染的易感性。我们的数据表明，ZIKV 促进其配体 Gas6 的上调，这有助于病毒感染性并推动 ZIKV 感染期间严重不良后果的发展。