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Parvovirus Capsid-Antibody Complex Structures Reveal Conservation of Antigenic Epitopes Across the Family
Viral Immunology ( IF 2.2 ) Pub Date : 2021-01-22 , DOI: 10.1089/vim.2020.0022
Shanan N Emmanuel 1 , Mario Mietzsch 1 , Yu Shan Tseng 1 , James Kennon Smith 1 , Mavis Agbandje-McKenna 1
Affiliation  

The parvoviruses are small nonenveloped single stranded DNA viruses that constitute members that range from apathogenic to pathogenic in humans and animals. The infection with a parvovirus results in the generation of antibodies against the viral capsid by the host immune system to eliminate the virus and to prevent re-infection. For members currently either being developed as delivery vectors for gene therapy applications or as oncolytic biologics for tumor therapy, efforts are aimed at combating the detrimental effects of pre-existing or post-treatment antibodies that can eliminate therapeutic benefits. Therefore, understanding antigenic epitopes of parvoviruses can provide crucial information for the development of vaccination applications and engineering novel capsids able to escape antibody recognition. This review aims to capture the information for the binding regions of ∼30 capsid-antibody complex structures of different parvovirus capsids determined to date by cryo-electron microscopy and three-dimensional image reconstruction. The comparison of all complex structures revealed the conservation of antigenic regions among parvoviruses from different genera despite low sequence identity and indicates that the available data can be used across the family for vaccine development and capsid engineering.

中文翻译:

细小病毒衣壳-抗体复合物结构揭示了整个家族中抗原表位的保守性

细小病毒是小的无包膜单链 DNA 病毒,其组成的成员范围从对人类和动物的无致病性到致病性不等。细小病毒感染导致宿主免疫系统产生针对病毒衣壳的抗体,以消除病毒并防止再次感染。对于目前正在开发作为基因治疗应用的递送载体或作为肿瘤治疗的溶瘤生物制剂的成员,努力旨在对抗可能消除治疗益处的预先存在或治疗后抗体的有害影响。因此,了解细小病毒的抗原表位可以为开发疫苗接种应用和设计能够逃避抗体识别的新型衣壳提供重要信息。本综述旨在捕获迄今为止通过冷冻电子显微镜和三维图像重建确定的不同细小病毒衣壳的约 30 种衣壳-抗体复合物结构的结合区域的信息。所有复杂结构的比较揭示了尽管序列同一性低,但来自不同属的细小病毒中抗原区域的保守性,并表明可用数据可用于整个家族的疫苗开发和衣壳工程。
更新日期:2021-01-28
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