Zika virus (ZIKV) has attracted the wide global attention due to its causal link to microcephaly. In this study, two amino acid (aa) mutation (E143K and R3394K) were identified at the fourth generation (named ZKC2P4) during the serial passage of ZIKV-Asian lineage ZKC2/2016 strain in the newborn mouse brain, while another seven aa deletions in envelope (E) protein were detected in ZKC2P6. ZKC2P6 is a novel nonglycosylated E protein Asian ZIKV we first identified and provides the first direct supporting evidence that glycosylation motif could be lost during the passage in neonatal mice. To study the impact of E protein glycosylation ablation, we compared the pathogenicity of ZKC2P6 with that of ZKC2P4. The results showed that the loss of E protein glycosylation accelerated the disease progression, as evidenced by an earlier weight loss and death, a thinner cerebral cortex, and more serious tissue lesions and inflammation/necrosis. Furthermore, ZKC2P6 exhibited a greater ability to replicate and caused severer cell apoptosis than that of ZKC2P4. Therefore, the ablation of E glycosylation generally enhances the neurovirulence of ZIKV and cell apoptosis in newborn mice.

中文翻译：

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包膜蛋白糖基化的消融增强了 ZIKV 的神经毒力和新生小鼠的细胞凋亡

寨卡病毒（ZIKV）因其与小头畸形的因果关系而引起全球广泛关注。在这项研究中，在 ZIKV-亚洲谱系 ZKC2/2016 品系在新生小鼠脑中连续传代期间，在第四代（命名为 ZKC2P4）鉴定了两个氨基酸 (aa) 突变（E143K 和 R3394K），而另外七个氨基酸缺失在 ZKC2P6 中检测到包膜 (E) 蛋白。ZKC2P6 是我们首次发现的一种新型非糖基化 E 蛋白亚洲 ZIKV，并提供了第一个直接支持证据，证明糖基化基序可能在新生小鼠的传代过程中丢失。为了研究 E 蛋白糖基化消融的影响，我们比较了 ZKC2P6 与 ZKC2P4 的致病性。结果表明，E蛋白糖基化的丧失加速了疾病的进展，早期体重减轻和死亡证明了这一点，更薄的大脑皮层，更严重的组织损伤和炎症/坏死。此外，与 ZKC2P4 相比，ZKC2P6 表现出更强的复制能力并导致更严重的细胞凋亡。因此，E糖基化的消除通常会增强ZIKV的神经毒力和新生小鼠的细胞凋亡。