Liu Yue, Wang Hong, Zhang Jun, Yang Jing, Bai Lu, Zheng Baisong, Zheng Tianhang, Wang Yingchao, Li Jianhua, Zhang Wenyan
Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
Department of Echocardiography, The First Hospital of Jilin University, Changchun, China.
Front Microbiol. 2020 Apr 30;11:697. doi: 10.3389/fmicb.2020.00697. eCollection 2020.
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.
丝氨酸整合蛋白3（SERINC3）和SERINC5最近被鉴定为针对人类免疫缺陷病毒1型（HIV-1）的宿主内在因子，并被HIV-1 Nef蛋白所拮抗。然而，它们是否抑制乙型肝炎病毒（HBV）（这是一个全球范围内严重的健康问题）尚不清楚。在此，我们证明SERINC5能有效抑制上清液中HBV病毒粒子的分泌，而不影响细胞内核心颗粒相关的DNA和总RNA，但SERINC3和SERINC1则无此作用。进一步研究发现，SERINC5增加了HBV的大蛋白（LHB）、中蛋白（MHB）和小蛋白（SHB）的非糖基化，并略微降低了表面抗原蛋白（HBs）水平，从而导致HBV分泌减少。重要的是，SERINC5与LHB蛋白在高尔基体中共定位，高尔基体对聚糖加工和转运很重要。此外，我们确定了SERINC5中抑制HBV所需的功能结构域，这与限制HIV-1所需的结构域完全不同，而SERINC5中的磷酸化和糖基化位点对于抑制HBV是可有可无的。综上所述，我们的结果表明，SERINC5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SERINC5可能具有广谱抗病毒活性。
