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在感染来自猿类的人畜共患病株的人类中,灵长类泡沫病毒包膜上的一个免疫显性和保守的 B 细胞表位被识别。

An Immunodominant and Conserved B-Cell Epitope in the Envelope of Simian Foamy Virus Recognized by Humans Infected with Zoonotic Strains from Apes.

机构信息

Unité d'Épidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France.

UMR CNRS 3569, Institut Pasteur, Paris, France.

出版信息

J Virol. 2019 May 15;93(11). doi: 10.1128/JVI.00068-19. Print 2019 Jun 1.

DOI:10.1128/JVI.00068-19
PMID:30894477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6532072/
Abstract

Cross-species transmission of simian foamy viruses (SFVs) from nonhuman primates (NHPs) to humans is currently ongoing. These zoonotic retroviruses establish lifelong persistent infection in their human hosts. SFV are apparently nonpathogenic , with ubiquitous tropism. Here, we aimed to identify envelope B-cell epitopes that are recognized following a zoonotic SFV infection. We screened a library of 169 peptides covering the external portion of the envelope from the prototype foamy virus (SFVpsc_huHSRV.13) for recognition by samples from 52 Central African hunters (16 uninfected and 36 infected with chimpanzee, gorilla, or SFV). We demonstrate the specific recognition of peptide N-V located in the leader peptide, gp18 Forty-three variant peptides with truncations, alanine substitutions, or amino acid changes found in other SFV species were tested. We mapped the epitope between positions 98 and 108 and defined six amino acids essential for recognition. Most plasma samples from SFV-infected humans cross-reacted with sequences from apes and Old World monkey SFV species. The magnitude of binding to peptide N-V was significantly higher for samples of individuals infected with a chimpanzee or gorilla SFV than those infected with a SFV. In conclusion, we have been the first to define an immunodominant B-cell epitope recognized by humans following zoonotic SFV infection. Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. SFVs can be transmitted to humans, in whom they establish persistent infection, like the simian lenti- and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 and human T-lymphotropic virus type 1. This is the first identification of an SFV-specific B-cell epitope recognized by human plasma samples. The immunodominant epitope lies in gp18, probably at the base of the envelope trimers. The NHP species the most genetically related to humans transmitted SFV strains that induced the strongest antibody responses. Importantly, this epitope is well conserved across SFV species that infect African and Asian NHPs.

摘要

灵长类动物源性泡沫病毒(SFV)从非人类灵长类动物(NHPs)向人类的跨物种传播目前正在进行中。这些人畜共患逆转录病毒在其人类宿主中建立终生持续性感染。SFV显然是无致病性的,具有普遍的嗜性。在这里,我们旨在鉴定在人畜共患 SFV 感染后被识别的包膜 B 细胞表位。我们筛选了来自原型泡沫病毒(SFVpsc_huHSRV.13)包膜外部的 169 个肽文库,以鉴定来自 52 名中非猎人(16 名未感染和 36 名感染黑猩猩、大猩猩或 SFV)的样本的识别。我们证明了位于引导肽 gp18 中的肽 N-V 的特异性识别。对 43 个具有截短、丙氨酸取代或在其他 SFV 物种中发现的氨基酸变化的变体肽进行了测试。我们将表位定位在 98 到 108 位之间,并定义了六个对识别至关重要的氨基酸。感染 SFV 的人类的大多数血浆样本与猿类和旧世界猴 SFV 物种的序列发生交叉反应。与感染 SFV 的个体相比,感染黑猩猩或大猩猩 SFV 的个体的样本与肽 N-V 的结合强度明显更高。总之,我们首次定义了人畜共患 SFV 感染后人类识别的免疫显性 B 细胞表位。泡沫病毒是已知最古老的逆转录病毒,在其自然动物宿主中主要被描述为非致病性。SFV 可以传播给人类,在人类中它们建立持续性感染,就像导致两种主要人类病原体人类免疫缺陷病毒 1 型和人类 T 淋巴细胞病毒 1 型出现的灵长类 lentiviruses 和 deltaviruses 一样。这是首次鉴定出人类血浆样本识别的 SFV 特异性 B 细胞表位。免疫显性表位位于 gp18 中,可能位于包膜三聚体的底部。与人类最具遗传关系的 NHPs 物种传播了诱导最强抗体反应的 SFV 株。重要的是,这个表位在感染非洲和亚洲 NHPs 的 SFV 物种中得到很好的保守。

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Potent neutralizing antibodies in humans infected with zoonotic simian foamy viruses target conserved epitopes located in the dimorphic domain of the surface envelope protein.在感染动物源性泡沫病毒的人类中发现的强效中和抗体针对位于表面包膜蛋白二聚体结构域中的保守表位。
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STLV-1 co-infection is correlated with an increased SFV proviral load in the peripheral blood of SFV/STLV-1 naturally infected non-human primates.STLV-1 合并感染与 SFV/STLV-1 自然感染的非人类灵长类动物外周血中 SFV 前病毒载量增加相关。
PLoS Negl Trop Dis. 2018 Oct 1;12(10):e0006812. doi: 10.1371/journal.pntd.0006812. eCollection 2018 Oct.
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When designing vaccines, consider the starting material: the human B cell repertoire.在设计疫苗时,要考虑起始材料:人类 B 细胞库。
Curr Opin Immunol. 2018 Aug;53:209-216. doi: 10.1016/j.coi.2018.08.002. Epub 2018 Sep 3.
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Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity.具有广泛 HIV-1 中和活性的个体具有独特的 IgG1 驱动的抗体反应特征。
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