SARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5.
SARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5.
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DOI：
10.1038/s41467-022-30609-9
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发表时间：
2022-05-26
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
丝氨酸蛋白酶5（SERINC 5）是一种参与鞘脂和磷脂酰丝氨酸生物合成的细胞多通道跨膜蛋白，有效地限制了许多逆转录病毒，包括人类免疫缺陷病毒（HIV）。SERINC 5被掺入出芽的病毒体中，导致病毒感染性的抑制。反过来，逆转录病毒，包括HIV，编码抵消SERINC 5抗病毒作用的因子。虽然SERINC 5在逆转录病毒中已经得到了很好的研究，但对其在其他病毒家族中的作用知之甚少。由于缺乏针对严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的宿主因子的信息，我们评估了SERINC蛋白对SARS-CoV-2感染的影响。在这里，我们发现SERINC 5通过阻断病毒-细胞融合来抑制SARS-CoV-2进入，SARS-CoV-2 ORF 7a通过阻断出芽病毒体中过度表达的SERINC 5的掺入来抵消SERINC 5的抗病毒作用。SERINC 5是一种参与鞘脂和磷脂酰丝氨酸生物合成的细胞多通道跨膜蛋白，也是一种已知的逆转录病毒限制因子。Timilsina等人的研究表明，SERINC 5是SARS-CoV-2的一种宿主限制因子，可阻止病毒在进入过程中融合。此外，他们显示病毒ORF 7a通过阻断SERINC 5并入子代病毒体来抵消SERINC 5抗病毒活性。
Serine Incorporator 5 (SERINC5), a cellular multipass transmembrane protein that is involved in sphingolipid and phosphatydilserine biogenesis, potently restricts a number of retroviruses, including Human Immunodeficiency Virus (HIV). SERINC5 is incorporated in the budding virions leading to the inhibition of virus infectivity. In turn, retroviruses, including HIV, encode factors that counteract the antiviral effect of SERINC5. While SERINC5 has been well studied in retroviruses, little is known about its role in other viral families. Due to the paucity of information regarding host factors targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), we evaluated the effect of SERINC proteins on SARS-CoV-2 infection. Here, we show SERINC5 inhibits SARS-CoV-2 entry by blocking virus-cell fusion, and SARS-CoV-2 ORF7a counteracts the antiviral effect of SERINC5 by blocking the incorporation of over expressed SERINC5 in budding virions. SERINC5, is a cellular multipass transmembrane protein involved in sphingolipid and phosphatydilserine biogenesis and a known retroviral restriction factor. Here, Timilsina et al. show that SERINC5 is a host restriction factor for SARS-CoV-2 that prevents viral fusion during entry. Further they show that viral ORF7a counteracts SERINC5 anti-viral activity by blocking its incorporation into progeny virions.
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