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鉴定对猪繁殖与呼吸综合征病毒(PRRSV)感染是必需的但不是与病毒包膜糖蛋白结合所必需的 CD163 区域。

Identification of CD163 regions that are required for porcine reproductive and respiratory syndrome virus (PRRSV) infection but not for binding to viral envelope glycoproteins.

机构信息

School of Medicine, Department of Medial Microbiology and Immunology, University of California Davis, Davis, CA, USA.

Department of Pathobiology, College of Veterinary Medicine Administration, University of Illinois at Urbana-Champaign, Champaign, IL, USA.

出版信息

Virology. 2022 Sep;574:71-83. doi: 10.1016/j.virol.2022.07.012. Epub 2022 Jul 31.

DOI:10.1016/j.virol.2022.07.012
PMID:35933832
Abstract

CD163, a receptor for porcine reproductive and respiratory syndrome virus (PRRSV), possesses nine scavenger receptor cysteine-rich (SRCR) and two proline-serine-threonine (PST) domains. To identify CD163 regions involved in PRRSV infection, CD163 mutants were generated. Infection experiments showed resistance to infection following deletion of the SRCR4/5 interdomain or the Exon 13 that encodes a portion of PSTII. The mutation of a pentapeptide domain in SRCR5 and SRCR7 also conferred resistance. Mutant CD163 proteins that resisted infection retained the ability to interact with GP2, GP3, GP4 and GP5 viral glycoproteins. The contribution of multiple domains to infection but not to the binding of viral glycoproteins suggests that the envelope proteins may form multiple interactions with CD163, or that receptor regions important for infection have other cellular binding partners required for PRRSV infection. Finally, we mapped the localization the anti-CD163 2A10 antibody epitope.

摘要

CD163 是猪繁殖与呼吸综合征病毒 (PRRSV) 的受体,它具有九个清道夫受体胱氨酸丰富 (SRCR) 和两个脯氨酸-丝氨酸-苏氨酸 (PST) 结构域。为了鉴定参与 PRRSV 感染的 CD163 区域,生成了 CD163 突变体。感染实验表明,删除 SRCR4/5 结构域或编码 PSTII 一部分的外显子 13 后,对感染具有抗性。SRCR5 和 SRCR7 中的五肽结构域的突变也赋予了抗性。抵抗感染的突变型 CD163 蛋白保留了与 GP2、GP3、GP4 和 GP5 病毒糖蛋白相互作用的能力。多个结构域对感染的贡献而不是对病毒糖蛋白结合的贡献表明,包膜蛋白可能与 CD163 形成多种相互作用,或者对感染很重要的受体区域具有 PRRSV 感染所需的其他细胞结合伙伴。最后,我们定位了抗 CD163 2A10 抗体表位。

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