牛SERINC5与牛白血病病毒细胞-细胞接触感染的相关性研究

Bovine leukemia virus (BLV), as a member of the retroviral family, could cause lymphoma formation in dairy cattle and thus lead to huge economic losses to the animal food production. However, vaccine candidates were less effective in controlling BLV infection. Currently, it was shown that host innate immunity factors (especially the membrane-associated factors) imposed multiple barriers for retroviral infection in vivo. SERINC5, as a newly identified host innate immunity factor, was unknown for its role in restricting BLV infection activity. Our initial results showed that bovine SERINC5 located at the cell membrane and could restrict retroviruses’ infectivity. In this study, we aimed to test bovine SERINC5 restriction activity on BLV infection using the in vitro cell-to-cell model. Further, we would also detect if BLV viral genes could regulate bovine cellular SERINC5 expression levels and thus resist its anti-viral activity. Based on these results, we could understand the role of membrane-associated factors on BLV infection and transmission, which would be beneficial for taking measures to enhance the host innate immunity to block BLV infection.

牛白血病病毒（BLV）是一种能引起牛慢性肿瘤的逆转录病毒，严重影响养牛业，但疫苗研发困难。天然免疫应答对逆转录病毒感染的限制发挥重要作用。然而，目前缺乏有关抗BLV感染天然免疫因子的研究。有研究表明，天然免疫限制因子SERINC5能够调控逆转录病毒的感染，且不同SERINC5剪接变异体对病毒感染的限制能力不同。本研究拟克隆牛SERINC5分子（含有两种剪接变异体），确定其在细胞内的定位，利用细胞-细胞接触感染模型研究牛SERINC5分子对BLV感染能力的调控。以此为基础，进一步明确BLV病毒蛋白能否通过调节牛SERINC5分子表达水平而拮抗其抗病毒活性，并尝试解析其可能机制。我们的研究结果有助于开发从天然免疫角度限制和阻断BLV对宿主细胞感染的方法，为有效的防控策略的手段提供思路，并为其他逆转录病毒领域天然免疫限制因子的研究提供借鉴。

丝氨酸整合酶SERINC5分子具有抗病毒活性，具体机制未知。本研究中，我们分别建立了人艾滋病病毒（HIV-1）和牛白血病病毒（BLV）的体外感染系统以探讨SERINC5分子的抗病毒机制。结果表明，人、牛和猫SERINC5分子能够限制HIV-1伪型病毒粒子游离感染，但不能限制HIV-1伪型病毒粒子和BLV病毒粒子细胞-细胞接触感染。BLV病毒囊膜糖蛋白的糖苷突变体介导的细胞-细胞接触感染对SERINC5分子抗病毒活性不敏感。这些结果表明，细胞-细胞接触感染有利于HIV-1和BLV跨越SERINC5分子的抗病毒限制效应，推测病毒可能利用这种机制逃逸其体内跨种属传播中SERINC5的复制限制。本研究可为后续宿主抗病毒分子的机制研究提供参考。