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Structural Perspectives of Beak and Feather Disease Virus and Porcine Circovirus Proteins
Viral Immunology ( IF 2.2 ) Pub Date : 2021-01-22 , DOI: 10.1089/vim.2020.0097
Babu Kanti Nath 1 , Shubhagata Das 1 , Justin A Roby 2 , Subir Sarker 3 , Daniel Luque 4 , Shane R Raidal 1 , Jade K Forwood 2
Affiliation  

Circoviruses represent a rapidly expanding group of viruses that infect both vertebrate and invertebrate hosts. Members are responsible for diseases of veterinary and economic importance, including postweaning multisystemic wasting syndrome in pigs, and beak and feather disease (BFD) in birds. These viruses are associated with lymphoid depletion and immunosuppressive conditions in infected animals leading to systemic illness. Circoviruses are small nonenveloped DNA viruses containing a single-stranded circular genome, encoding two major proteins: the capsid-associated protein (Cap), comprising the entirety of the viral capsid, and the replication-associated protein (Rep). Cap is the only protein component of the virion and plays crucial roles throughout the virus replication cycle, including viral attachment, cell entry, genome uncoating, and packaging of newly formed viral particles. Rep mediates recognition of replication origin motifs in the viral genome sequence and is responsible for endonuclease activity enabling nicking of the circular DNA and initiation of rolling-circle replication (RCR). Porcine circovirus 2 (PCV2) was the first circovirus capsid structure to be solved at atomic resolution using X-ray crystallography. The structure revealed an assembly comprising 60 monomeric subunits to form virus-like particles. Each Cap monomer harbors a canonical viral jelly roll domain composed of two, four-stranded antiparallel β-sheets. Crystal structures of two distinct macromolecular assemblies from BFD virus Cap were also resolved at high resolution. In these structures, the exposure of the N-terminal arginine-rich motif, responsible for DNA binding and nuclear localization is reversed. Additional structural investigations have also elucidated a PCV2 type-specific neutralizing epitope, and interaction between the PCV2 capsid and polymers such as heparin. In this review, we provide a snapshot of the structural and functional aspects of circovirus proteins.

中文翻译:

喙羽病病毒和猪圆环病毒蛋白的结构前景

圆环病毒代表了一组迅速扩大的病毒,它们同时感染脊椎动物和无脊椎动物宿主。成员负责对兽医和经济具有重要意义的疾病,包括猪的断奶后多系统消耗综合征和鸟类的喙和羽毛病 (BFD)。这些病毒与受感染动物的淋巴耗竭和免疫抑制状况有关,从而导致全身性疾病。圆环病毒是含有单链环状基因组的小型无包膜 DNA 病毒,编码两种主要蛋白质:包括整个病毒衣壳的衣壳相关蛋白 (Cap) 和复制相关蛋白 (Rep)。Cap 是病毒粒子的唯一蛋白质成分,在整个病毒复制周期中起着至关重要的作用,包括病毒附着、细胞进入、基因组脱壳、以及新形成的病毒颗粒的包装。Rep 介导病毒基因组序列中复制起点基序的识别,并负责核酸内切酶活性,使环状 DNA 产生切口并启动滚环复制 (RCR)。猪圆环病毒 2 (PCV2) 是第一个使用 X 射线晶体学以原子分辨率解​​析的圆环病毒衣壳结构。该结构揭示了一个包含 60 个单体亚基的组件,以形成病毒样颗粒。每个 Cap 单体都含有一个典型的病毒果冻卷结构域,该结构域由两个四链反平行链组成 猪圆环病毒 2 (PCV2) 是第一个使用 X 射线晶体学以原子分辨率解​​析的圆环病毒衣壳结构。该结构揭示了一个包含 60 个单体亚基的组件,以形成病毒样颗粒。每个 Cap 单体都含有一个典型的病毒果冻卷结构域,该结构域由两个四链反平行链组成 猪圆环病毒 2 (PCV2) 是第一个使用 X 射线晶体学以原子分辨率解​​析的圆环病毒衣壳结构。该结构揭示了一个包含 60 个单体亚基的组件,以形成病毒样颗粒。每个 Cap 单体都含有一个典型的病毒果冻卷结构域,该结构域由两个四链反平行链组成β-折叠。来自 BFD 病毒 Cap 的两种不同大分子组装体的晶体结构也以高分辨率解析。在这些结构中,负责 DNA 结合和核定位的 N 末端富含精氨酸的基序的暴露被逆转。额外的结构研究还阐明了 PCV2 类型特异性中和表位,以及 PCV2 衣壳与肝素等聚合物之间的相互作用。在这篇综述中,我们简要介绍了圆环病毒蛋白的结构和功能方面。
更新日期:2021-01-28
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