Structure of infective Getah virus at 2.8 Å resolution determined by cryo-electron microscopy.

Structure of infective Getah virus at 2.8 Å resolution determined by cryo-electron microscopy.
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通过冷冻电子显微镜确定 2.8 × 分辨率的感染性 Getah 病毒的结构

DOI:
10.1038/s41421-022-00374-6
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发表时间:
2022-02-11
期刊:
影响因子:
33.5
通讯作者:
Liu Z
Liu Z
中科院分区:
生物学1区
文献类型:
--
作者:
Wang A;Zhou F;Liu C;Gao D;Qi R;Yin Y;Liu S;Gao Y;Fu L;Xia Y;Xu Y;Wang C;Liu Z

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盖塔病毒 (GETV) 是甲病毒属的一员,是一种蚊媒病原体,可导致动物发热和繁殖损失。尽管在超过 10% 的健康人体内发现了 GETV 抗体,但目前还没有与 GETV 相关的临床症状的报道。 GETV 的生物学和病理学特性很大程度上未知,并且由于缺乏对 GETV 病毒颗粒结构的了解,针对 GETV 的抗病毒或疫苗治疗仍然无法获得。在这里,我们以 2.8 Å 的分辨率展示了感染性 GETV 的结构,以及衣壳蛋白和包膜糖蛋白 E1 和 E2 的原子模型。我们在 E1 和 E2 中鉴定出了许多糖基化和 S-酰化位点。表面暴露的聚糖表明可能对病毒免疫逃避和宿主细胞入侵产生影响。 S-酰化位点可能参与稳定 E1 和 E2 的跨膜组装。此外,在跨膜疏水口袋中观察到胆固醇和磷脂分子,以及口袋周围的另外两个胆固醇。胆固醇和磷脂稳定病毒包膜中的疏水袋。结构信息将有助于基于结构的抗病毒和疫苗筛选、设计和优化。
Getah virus (GETV), a member of the genus alphavirus, is a mosquito-borne pathogen that can cause pyrexia and reproductive losses in animals. Although antibodies to GETV have been found in over 10% of healthy people, there are no reports of clinical symptoms associated with GETV. The biological and pathological properties of GETV are largely unknown and antiviral or vaccine treatments against GETV are still unavailable due to a lack of knowledge of the structure of the GETV virion. Here, we present the structure of infective GETV at a resolution of 2.8 Å with the atomic models of the capsid protein and the envelope glycoproteins E1 and E2. We have identified numerous glycosylation and S-acylation sites in E1 and E2. The surface-exposed glycans indicate a possible impact on viral immune evasion and host cell invasion. The S-acylation sites might be involved in stabilizing the transmembrane assembly of E1 and E2. In addition, a cholesterol and a phospholipid molecule are observed in a transmembrane hydrophobic pocket, together with two more cholesterols surrounding the pocket. The cholesterol and phospholipid stabilize the hydrophobic pocket in the viral envelope membrane. The structural information will assist structure-based antiviral and vaccine screening, design, and optimization.
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