Department of Medical Research, Taipei Veterans General Hospital and Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
J Med Virol. 2019 Oct;91(10):1743-1750. doi: 10.1002/jmv.25518. Epub 2019 Jul 10.
BST2/tetherin, an interferon-inducible antiviral factor, can block the cellular release of various enveloped viruses. We previously reported that human coronavirus 229E (HCoV-229E) infection can alleviate the BST2 tethering of HIV-1 virions by downregulating cell surface BST2, suggesting that coronaviruses are capable of encoding anti-BST2 factors. Here we report our new finding that severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) glycoprotein, similar to Vpu, is capable of antagonizing the BST2 tethering of SARS-CoV, HCoV-229E, and HIV-1 virus-like particles via BST2 downregulation. However, unlike Vpu (which downmodulates BST2 by means of proteasomal and lysosomal degradation pathways), BST2 downregulation is apparently mediated by SARS-CoV S through the lysosomal degradation pathway only. We found that SARS-CoV S colocalized with both BST2 and reduced cell surface BST2, suggesting an association between SARS-CoV S and BST2 that targets the lysosomal degradation pathway. According to one recent report, SARS-CoV ORF7a antagonizes BST2 by interfering with BST2 glycosylation . Our data provide support for the proposal that SARS-CoV and other enveloped viruses are capable of evolving supplementary anti-BST2 factors in a manner that requires virus replication. Further experiments are required to determine whether the BST2-mediated restriction of authentic SARS-CoV virions is alleviated by the SARS-CoV spike protein.
BST2/tetherin 是一种干扰素诱导的抗病毒因子，可以阻止各种包膜病毒的细胞释放。我们之前曾报道，人类冠状病毒 229E（HCoV-229E）感染可以通过下调细胞表面 BST2 来减轻 HIV-1 病毒粒子的 BST2 束缚，这表明冠状病毒能够编码抗 BST2 因子。在这里，我们报告了一项新发现，即严重急性呼吸综合征冠状病毒（SARS-CoV）刺突（S）糖蛋白与 Vpu 相似，能够通过下调 BST2 拮抗 SARS-CoV、HCoV-229E 和 HIV-1 病毒样颗粒的 BST2 束缚。然而，与 Vpu（通过蛋白酶体和溶酶体降解途径下调 BST2）不同，BST2 的下调显然是通过 SARS-CoV S 通过溶酶体降解途径介导的。我们发现 SARS-CoV S 与 BST2 和减少的细胞表面 BST2 共定位，表明 SARS-CoV S 与 BST2 之间存在关联，该关联靶向溶酶体降解途径。根据最近的一份报告，SARS-CoV ORF7a 通过干扰 BST2 糖基化来拮抗 BST2。我们的数据支持了这样一种观点，即 SARS-CoV 和其他包膜病毒能够以需要病毒复制的方式进化出补充的抗 BST2 因子。需要进一步的实验来确定 SARS-CoV 刺突蛋白是否减轻了 BST2 介导的对真实 SARS-CoV 病毒粒子的限制。
