SERINC5 Inhibits the Secretion of Complete and Genome-Free Hepatitis B Virions Through Interfering With the Glycosylation of the HBV Envelope
SERINC5 Inhibits the Secretion of Complete and Genome-Free Hepatitis B Virions Through Interfering With the Glycosylation of the HBV Envelope
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DOI：
10.3389/fmicb.2020.00697
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发表时间：
2020-04-30
影响因子：
5.2
通讯作者：
Zhang, Wenyan
中科院分区：
文献类型：
--
作者：
Liu, Yue;Wang, Hong;Zhang, Wenyan
丝氨酸蛋白酶3（Serine Apoptosis 3，SERINC 3）和丝氨酸蛋白酶5（Serine Apoptosis 5，SERINC 5）是近年来发现的抗人类免疫缺陷病毒（human immunodeficiency virus，HIV-1）的宿主内源性因子。然而，它们是否抑制B型肝炎病毒（HBV），这是一个严重的健康问题，在世界范围内，是未知的。在这里，我们证明，SERINC 5有效地抑制HBV病毒粒子分泌的上清液中，而不影响细胞内核心颗粒相关的DNA和总RNA，但SERINC 3和SERINC 1没有。进一步的研究发现SERINC 5增加了HBV的LHB、MHB和SHB蛋白的非糖基化，并轻微降低了HBs蛋白水平，从而导致HBV分泌减少。重要的是，SERINC 5与高尔基体中的LHB蛋白共定位，这对聚糖加工和运输很重要。此外，我们确定了SERINC 5中HBV抑制所需的功能结构域，这与HIV-1限制所需的功能结构域完全不同，而SERINC 5中的磷酸化和糖基化位点与HBV限制无关。综上所述，我们的研究结果表明，SERINC 5通过干扰HBV蛋白的糖基化来抑制HBV病毒粒子的分泌，这表明SERINC 5可能具有广谱抗病毒活性。
Serine incorporator 3 (SERINC3) and SERINC5 were recently identified as host intrinsic factors against human immunodeficiency virus (HIV)-1 and counteracted by HIV-1 Nef. However, whether they inhibit hepatitis B virus (HBV), which is a severe health problem worldwide, is unknown. Here, we demonstrate that SERINC5 potently inhibited HBV virion secretion in the supernatant without affecting intracellular core particle-associated DNA and the total RNA, but SERINC3 and SERINC1 did not. Further investigation discovered that SERINC5 increased the non-glycosylation of LHB, MHB, and SHB proteins of HBV and slightly decreased HBs proteins levels, which led to the decreased HBV secretion. Importantly, SERINC5 co-localized with LHB proteins in the Golgi apparatus, which is important for glycan processing and transport. In addition, we determined the functional domain in SERINC5 required for HBV inhibition, which was completely different from that required for HIV-1 restriction, whereas phosphorylation and glycosylation sites in SERINC5 were dispensable for HBV restriction. Taken together, our results demonstrate that SERINC5 suppresses HBV virion secretion through interfering with the glycosylation of HBV proteins, suggesting that SERINC5 might possess broad-spectrum antiviral activity.