SERINC5通过干扰HBV信封的糖基化抑制完全和无基因组的乙型肝

StephenW

SERINC5 Inhibits the Secretion of Complete and Genome-Free Hepatitis B Virions Through Interfering With the Glycosylation of the HBV Envelope
Yue Liu  1   2 , Hong Wang  1 , Jun Zhang  1 , Jing Yang  1 , Lu Bai  3 , Baisong Zheng  1 , Tianhang Zheng  1 , Yingchao Wang  4 , Jianhua Li  3 , Wenyan Zhang  1
Affiliations
Affiliations

    1
    Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
    2
    Department of Echocardiography, The First Hospital of Jilin University, Changchun, China.
    3
    Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
    4
    Department of Hepatobiliary Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China.

    PMID: 32431673 PMCID: PMC7216740 DOI: 10.3389/fmicb.2020.00697

Abstract

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.

Keywords: glycosylation; hepatitis B virus (HBV); host–pathogen interaction; inhibitory mechanism; secretion; serine incorporator 5 (SERINC5).

Copyright © 2020 Liu, Wang, Zhang, Yang, Bai, Zheng, Zheng, Wang, Li and Zhang.

StephenW

SERINC5通过干扰HBV信封的糖基化抑制完全和无基因组的乙型肝炎病毒的分泌
刘悦1 2，王宏1，张军1，景阳1，鲁白3，百松正1，天航正1，王应超4，李建华3，张文彦1
隶属关系
隶属关系

1个
吉林大学第一医院病毒与艾滋病研究所，长春
2
吉林大学第一医院心动图科，长春
3
复旦大学上海医学院基础医学学院，教育与卫生部医学分子病毒学重点实验室，上海
4
吉林大学第一医院肝胆胰外科，长春

PMID：32431673 PMCID：PMC7216740 DOI：10.3389 / fmicb.2020.00697

抽象

最近发现，丝氨酸掺入剂3（SERINC3）和SERINC5是抵抗人类免疫缺陷病毒（HIV）-1的宿主内在因素，并被HIV-1 Nef所抵消。但是，它们是否抑制乙型肝炎病毒（HBV），这是世界范围内严重的健康问题，目前还不得而知。在这里，我们证明SERINC5可以有效抑制上清液中的HBV病毒粒子分泌，而不会影响细胞内核心颗粒相关的DNA和总RNA，但SERINC3和SERINC1则不然。进一步的研究发现SERINC5增加了HBV的LHB，MHB和SHB蛋白的非糖基化，并稍微降低了HBs蛋白的水平，从而导致HBV分泌减少。重要的是，SERINC5与高尔基体中的LHB蛋白共定位，这对聚糖的加工和运输很重要。此外，我们确定了SERINC5中抑制HBV所需的功能域，该功能域与HIV-1限制所需的功能域完全不同，而SERINC5中的磷酸化和糖基化位点对于HBV限制是可有的。两者合计，我们的结果表明SERINC5通过干扰HBV蛋白的糖基化抑制HBV病毒粒子的分泌，这表明SERINC5可能具有广谱抗病毒活性。

关键词：糖基化；乙型肝炎病毒（HBV）；宿主-病原体相互作用；抑制机制分泌;丝氨酸掺入剂5（SERINC5）。

版权所有©2020 Liu，Wang，Zhang，Yang，Bai，Zheng，Zheng，Wang，Li and Zhang。

StephenW

https://pubmed.ncbi.nlm.nih.gov/ ... ge=2&from_pos=1