Riga Stradins University, Institute of Microbiology and Virology, Riga, Latvia.
Riga East Clinical University Hospital, Clinic "Gailezers", Riga, Latvia.
Microbiol Spectr. 2022 Jun 29;10(3):e0236921. doi: 10.1128/spectrum.02369-21. Epub 2022 May 23.
Human herpesvirus-6 (HHV-6) contains two genes (U12 and U51) that encode putative homologues of human G-protein-coupled receptors like CCR1, CCR3, and CCR5. It has been shown that these viral proteins can be expressed on the surface of epithelial and some peripheral blood mononuclear cells, suggesting that they could potentially induce autoimmunity. We aimed to investigate the possibility of HHV-6 encoded viral chemokine receptors (U12 and U51) involvement in autoimmune thyroiditis (AIT) development by detecting viral peptide specific antibodies in AIT patient samples. Seventy-nine AIT patients whose thyroid tissues were shown to be positive for HHV-6 and 32 blood donors were enrolled in this study. Twenty-eight synthetic peptides derived from HHV-6 U12 and U51 proteins' amino acid sequences, as well as recombinant human CCR1, CCR3, and CCR5 proteins were used in suspension multiplex immunological assay to detect specific IgG and IgM antibodies. HHV-6 peptide specific IgG and IgM antibodies were found in patients' samples. AIT patients' samples were found to be more frequently positive for peptide IgGs in comparison to control group's samples. Even though peptide antibody cross-reactivity with human CCRs was not demonstrated, our results show a new immunogenic HHV-6 antigen-a possible new player in the HHV-6 induced autoimmunity exacerbation. The study of human herpesvirus-6 (HHV-6) involvement in autoimmunity development is very challenging, due to the complex nature of this virus. HHV-6 is a ubiquitous, lifelong persistent, and immunomodulating virus, which mainly spreads in solid tissues using cell-to-cell mechanics, and thus can escape from the host's immune response. It has been implicated as an environmental factor in several autoimmune diseases. An association between HHV-6 and autoimmune thyroiditis has been demonstrated, yet clear mechanism of involvement remains to be elucidated, since the virus can be detected in nearly all autoimmune thyroiditis patient thyroid glands. Our results show new potentially immunogenic human herpesvirus-6 antigens-possible new players in the HHV-6 induced autoimmunity exacerbation, which could be subjects for further research. Together with previously published results, this study described possible mechanisms which may underlie the induction of autoimmune reactivities against thyroid tissues in AIT.
人类疱疹病毒-6（HHV-6）包含两个基因（U12 和 U51），它们编码类似于 CCR1、CCR3 和 CCR5 的人类 G 蛋白偶联受体的假定同源物。已经表明，这些病毒蛋白可以在上皮细胞和一些外周血单核细胞的表面表达，这表明它们可能潜在地诱导自身免疫。我们旨在通过检测 AIT 患者样本中的病毒肽特异性抗体，研究 HHV-6 编码的病毒趋化因子受体（U12 和 U51）是否参与自身免疫性甲状腺炎（AIT）的发展。本研究纳入了 79 名甲状腺组织显示 HHV-6 阳性的 AIT 患者和 32 名献血者。使用悬浮式多重免疫分析检测 28 种源自 HHV-6 U12 和 U51 蛋白氨基酸序列的合成肽以及重组人 CCR1、CCR3 和 CCR5 蛋白，以检测特异性 IgG 和 IgM 抗体。在患者样本中发现了 HHV-6 肽特异性 IgG 和 IgM 抗体。与对照组样本相比，AIT 患者样本中发现肽 IgG 更为常见。尽管未证明肽抗体与人 CCR 之间存在交叉反应，但我们的结果表明 HHV-6 是一种新的免疫原性抗原，可能是 HHV-6 诱导自身免疫加重的新参与者。研究人类疱疹病毒-6（HHV-6）在自身免疫发展中的作用非常具有挑战性，因为该病毒的性质非常复杂。HHV-6 是一种普遍存在、终生持续存在且具有免疫调节作用的病毒，主要通过细胞间机制在实体组织中传播，因此可以逃避宿主的免疫反应。它已被认为是几种自身免疫性疾病的环境因素。已经证明 HHV-6 与自身免疫性甲状腺炎之间存在关联，但参与的明确机制仍有待阐明，因为该病毒几乎可以在所有自身免疫性甲状腺炎患者的甲状腺中检测到。我们的结果表明，HHV-6 存在新的潜在免疫原性抗原，可能是 HHV-6 诱导自身免疫加重的新参与者，这可能是进一步研究的对象。结合之前发表的结果，本研究描述了可能的机制，这些机制可能是 AIT 中甲状腺组织自身免疫反应诱导的基础。
