Comparative Medicine Center, Peking Union Medical College (PUMC) and, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China.
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing 100021, China.
J Immunol Res. 2021 Jul 16;2021:5317662. doi: 10.1155/2021/5317662. eCollection 2021.
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.
寨卡病毒（Zika virus，ZIKV）因其与小头症的因果关系而引起了全球广泛关注。在本研究中，在 ZIKV-亚洲谱系 ZKC2/2016 株在新生小鼠脑中的连续传代过程中发现了第 4 代的两个氨基酸（aa）突变（E143K 和 R3394K）（命名为 ZKC2P4），而包膜（E）蛋白中另外七个 aa 缺失则在 ZKC2P6 中检测到。ZKC2P6 是我们首次鉴定的新型非糖基化 E 蛋白亚洲 ZIKV，为糖基化基序可能在新生小鼠传代过程中丢失提供了首个直接证据。为了研究 E 蛋白糖基化缺失的影响，我们比较了 ZKC2P6 与 ZKC2P4 的致病性。结果表明，E 蛋白糖基化的缺失加速了疾病的进展，表现在体重减轻和死亡更早、大脑皮层更薄、组织损伤和炎症/坏死更严重。此外，ZKC2P6 的复制能力更强，引起的细胞凋亡比 ZKC2P4 更严重。因此，E 糖基化的缺失通常会增强 ZIKV 在新生小鼠中的神经毒力和细胞凋亡。
