Atomic Structure of the Human Sapovirus Capsid Reveals a Unique Capsid Protein Conformation in Caliciviruses.
Atomic Structure of the Human Sapovirus Capsid Reveals a Unique Capsid Protein Conformation in Caliciviruses.
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DOI：
10.1128/jvi.00298-22
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发表时间：
2022-05-11
影响因子：
5.4
通讯作者：
Murata, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Miyazaki, Naoyuki;Song, Chihong;Oka, Tomoichiro;Miki, Motohiro;Murakami, Kosuke;Iwasaki, Kenji;Katayama, Kazuhiko;Murata, Kazuyoshi
关键词：
Sapovirus（SaV）是杯状病毒科（Caliciviridae）的成员，其引起人类和动物的急性胃肠炎。人痘病毒（HuSaV）具有遗传和抗原多样性，但缺乏病毒复制系统和结构信息阻碍了疫苗和治疗剂的开发。在这里，我们成功地从HuSaV GI.6 VP 1蛋白中产生了自组装的病毒样颗粒（VLP），并使用单颗粒冷冻电子显微镜（cryo-EM）以2.9-nm的分辨率确定了第一个原子结构。VP 1蛋白的原子模型揭示了杯状病毒中独特的衣壳蛋白构象。A、B和C亚基中的所有N-末端臂在延伸穿过它们的亚基后与相邻的壳结构域相互作用。弓形VP 1二聚体的顶部由相互连接的β链和环在P2亚结构域之间形成，与其他杯状病毒相比，其掩埋表面最小化。四个高变区，可能参与SaV的抗原多样性形成广泛的集群上的P结构域。潜在的受体结合区暗示的组织培养突变体的猪SaV也位于这些高变簇附近。VP 1蛋白的保守序列基序“PPG”和“GWS”可分别稳定内衣壳壳和外突出结构域。这些发现将为HuSaV感染的医学治疗提供结构基础，并促进疫苗，抗病毒药物和诊断系统的开发。重要性SaV和诺如病毒属于杯状病毒科，是人类和动物急性胃肠炎的常见原因。SaV和诺如病毒感染是所有年龄组的公共卫生问题，在世界范围内呈爆发性和零星发生。HuSaV在遗传和抗原性上是多样的，并且基于VP 1蛋白的序列相似性，目前将其分为由18种基因型组成的4个基因组。尽管有这些详细的遗传分析，但缺乏病毒衣壳的结构信息已成为疫苗或抗病毒药物开发的一个问题。本文提出的HuSaV GI.6 VLP的2.9-ε原子模型不仅揭示了参与免疫应答和潜在受体结合位点的氨基酸残基的位置，而且还为开发疫苗和抗病毒药所需的稳定构建体的设计提供了重要信息。
Sapovirus (SaV) is a member of the Caliciviridae family, which causes acute gastroenteritis in humans and animals. Human sapoviruses (HuSaVs) are genetically and antigenically diverse, but the lack of a viral replication system and structural information has hampered the development of vaccines and therapeutics. Here, we successfully produced a self-assembled virus-like particle (VLP) from the HuSaV GI.6 VP1 protein, and the first atomic structure was determined using single-particle cryo-electron microscopy (cryo-EM) at a 2.9-Å resolution. The atomic model of the VP1 protein revealed a unique capsid protein conformation in caliciviruses. All N-terminal arms in the A, B, and C subunits interacted with adjacent shell domains after extending through their subunits. The roof of the arched VP1 dimer was formed between the P2 subdomains by the interconnected β strands and loops, and its buried surface was minimized compared to those of other caliciviruses. Four hypervariable regions that are potentially involved in the antigenic diversity of SaV formed extensive clusters on top of the P domain. Potential receptor binding regions implied by tissue culture mutants of porcine SaV were also located near these hypervariable clusters. Conserved sequence motifs of the VP1 protein, “PPG” and “GWS,” may stabilize the inner capsid shell and the outer protruding domain, respectively. These findings will provide the structural basis for the medical treatment of HuSaV infections and facilitate the development of vaccines, antivirals, and diagnostic systems. IMPORTANCE SaV and norovirus, belonging to the Caliciviridae family, are common causes of acute gastroenteritis in humans and animals. SaV and norovirus infections are public health problems in all age groups, which occur explosively and sporadically worldwide. HuSaV is genetically and antigenically diverse and is currently classified into 4 genogroups consisting of 18 genotypes based on the sequence similarity of the VP1 proteins. Despite these detailed genetic analyses, the lack of structural information on viral capsids has become a problem for the development of vaccines or antiviral drugs. The 2.9-Å atomic model of the HuSaV GI.6 VLP presented here not only revealed the location of the amino acid residues involved in immune responses and potential receptor binding sites but also provided essential information for the design of stable constructs needed for the development of vaccines and antivirals.
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影响因子：
48
作者：
Li, Xueming;Mooney, Paul;Zheng, Shawn;Booth, Christopher R.;Braunfeld, Michael B.;Gubbens, Sander;Agard, David A.;Cheng, Yifan
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影响因子：
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作者：
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
56.9
作者：
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通讯作者：
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O连接糖蛋白上的α2,3-和α2,6-连接的唾液酸都作为猪Sapovirus的功能受体。
影响因子：
6.7
作者：
Kim DS;Hosmillo M;Alfajaro MM;Kim JY;Park JG;Son KY;Ryu EH;Sorgeloos F;Kwon HJ;Park SJ;Lee WS;Cho D;Kwon J;Choi JS;Kang MI;Goodfellow I;Cho KO
通讯作者：
Cho KO