Linear epitopes of PRRSV-1 envelope proteins ectodomains are not correlated with broad neutralization.

IF 3 2区 农林科学 Q1 VETERINARY SCIENCES
Jaime Castillo-Pérez, Francisco Javier Martínez-Lobo, Raquel Frómeta, José María Castro, Isabel Simarro, Cinta Prieto
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引用次数: 0

Abstract

Background: Neutralizing antibodies against PRRSV are capable of conferring protection against viral reinfection, but they tend to be strain specific and usually have poor cross-reactivity. Nonetheless, it has been described that there are individuals capable of efficiently neutralizing viruses of different origin, so it is expected that there are conserved neutralizing epitopes relevant for broad neutralization. However, although immunodominant regions and neutralizing epitopes have been described in different envelope proteins, their role in broad neutralization is unknown. The main objective of this study was to determine whether the linear epitopes existing in the ectodomains of PRRSV envelope proteins play a role in cross-neutralization.

Results: A pepscan analysis was carried out using synthetic peptides against the ectodomains of PRRSV envelope proteins and PRRSV-hyperimmune sera of different cross-reactivity. The results obtained confirm the existence of antigenic regions in the ectodomains of the GP2, GP3, GP4 and GP5 that tend to be relatively conserved among different PRRSV isolates. Nonetheless, these antigenic regions have poor immunogenicity since they are only recognized by a limited number of sera. Furthermore, no differences were found between the reactivity of sera with broad cross-neutralization capacity and sera with poor heterologous neutralization activity, which indicate that linear epitopes existing in the ectodomains of PRRSV envelope proteins are not relevant for the development of broadly reactive neutralizing antibodies. Subsequently, some selected peptides were used in competition assays with the virus for binding to the cell receptors and in seroneutralization inhibition assays by incubation with hyperimmune sera. Firstly, some peptides that interfere with virus infectivity were identified in competition assays, but only in the case of one viral isolate, which points to the possible existence of a strain-dependent inhibition. However, the results of the seroneutralization inhibition assay indicate that, under the conditions of our study, none of the peptides used was capable of inhibiting virus neutralization by the hyperimmune sera.

Conclusions: The results obtained indicate that the linear peptides analyzed in this study do not play a major role in the induction of broadly reactive neutralizing antibodies, which could probably depend on conformational neutralizing.

PRRSV-1 包膜蛋白外显子的线性表位与广泛中和无关。
背景:针对 PRRSV 的中和抗体能够对病毒再感染起到保护作用,但它们往往具有毒株特异性,通常交叉反应性较差。然而,据描述,有些个体能够有效中和不同来源的病毒,因此预计存在与广泛中和相关的保守中和表位。然而,虽然不同包膜蛋白中的免疫优势区和中和表位已被描述,但它们在广泛中和中的作用尚不清楚。本研究的主要目的是确定存在于 PRRSV 包膜蛋白外结构域中的线性表位是否在交叉中和中发挥作用:使用针对 PRRSV 包膜蛋白外结构域的合成肽和具有不同交叉反应性的 PRRSV 高免疫血清进行了 pepscan 分析。结果证实,GP2、GP3、GP4 和 GP5 外显子中存在抗原区,这些抗原区在不同的 PRRSV 分离物中往往相对保守。然而,这些抗原区的免疫原性很差,因为只有少数血清能识别它们。此外,具有广泛交叉中和能力的血清与异源中和活性差的血清之间的反应性没有差异,这表明存在于 PRRSV 包膜蛋白外显子中的线性表位与开发具有广泛反应性的中和抗体无关。随后,研究人员将筛选出的一些多肽用于与病毒结合细胞受体的竞争试验,以及与超免疫血清孵育的血清中和抑制试验。首先,在竞争试验中发现了一些干扰病毒感染性的多肽,但只在一种病毒分离物中发现了这种多肽,这表明可能存在毒株依赖性抑制。然而,血清中和抑制试验的结果表明,在我们的研究条件下,所使用的肽都不能抑制超免疫血清对病毒的中和作用:结论:研究结果表明,本研究分析的线性肽在诱导广泛反应性中和抗体中没有发挥主要作用,这可能取决于构象中和。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Porcine Health Management
Porcine Health Management Veterinary-Food Animals
CiteScore
5.40
自引率
5.90%
发文量
49
审稿时长
14 weeks
期刊介绍: Porcine Health Management (PHM) is an open access peer-reviewed journal that aims to publish relevant, novel and revised information regarding all aspects of swine health medicine and production.
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