Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers.
Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers.
复制标题
HIV精英控制器中的抗HERV-K（HML-2）衣壳抗体反应。
DOI：
10.1186/s12977-017-0365-2
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发表时间：
2017-08-22
期刊：
影响因子：
3.3
通讯作者：
Michaud HA
中科院分区：
文献类型：
--
作者：
de Mulder M;SenGupta D;Deeks SG;Martin JN;Pilcher CD;Hecht FM;Sacha JB;Nixon DF;Michaud HA
人类内源性逆转录病毒（HERV）约占人类基因组的8%，虽然大多数是转录沉默的，但最近整合的HERV， HERV- k （HML-2）仍然具有活性。在HIV感染期间，可以检测到HERV-K （HML-2）特异性mRNA转录物和病毒蛋白。在这项研究中，我们的目的是了解在HIV-1感染背景下针对HERV-K (HML-2) Gag的抗体反应。我们开发了一种ELISA方法，使用重组蛋白或164个冗余的“15mer”HERV-K (HML-2) Gag肽来检测血清的抗体反应性。我们共鉴定出8个潜在的HERV-K (HML-2) Gag免疫原性结构域：2个在基质上（肽16和31），1个在p15上（肽85），3个在衣壳上（肽81、97和117），1个在核衣壳上（肽137），1个在QP1蛋白上（肽157）。4个表位（肽16、31、85和137）具有高免疫原性。在测试的8个表位中的6个中，在HIV感染的参与者（n = 40）和未感染的供者（n = 40）之间的抗体反应没有发现显著差异。与未感染hiv的个体相比，hiv感染成人对核衣壳（肽137）的抗体应答显著降低（p < 0.001），而对QP1（肽157）的抗体应答显著提高（p < 0.05）。在艾滋病毒感染者中，未经治疗的控制艾滋病毒的个体（“精英”控制者）对p15蛋白（肽85）的应答水平明显低于未经治疗的非控制者（p < 0.05）和未感染的供者（p < 0.05）。相比之下，控制者对衣壳蛋白（表位81和117）的反应明显高于未感染的供者（p分别< 0.001和<0.05）和非控制者（p < 0.01和<0.05）。在γ干扰素（IFN-γ）酶免疫斑点（Elispot）检测中，研究参与者外周血单个核细胞（PBMCs）对HERV-K （HML-2）衣壳重组肽的反应。Elispot检测发现HERV-K (HML-2) Gag抗体与T细胞应答显著相关。HIV精英控制者对HERV-K (HML-2) Gag具有强烈的细胞和抗体反应，主要针对衣壳区。总的来说，这些数据表明靶向衣壳的抗herv - k （HML-2）抗体可能在HIV感染中具有免疫保护作用。本文的在线版本（doi:10.1186/s12977-017-0365-2）包含补充材料，可供授权用户使用。
Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection. We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on the matrix (peptides 16 and 31), one on p15 (peptide 85), three on the capsid (peptides 81, 97 and 117), one on the nucleocapsid (peptide 137) and one on the QP1 protein (peptide 157). Four epitopes (peptides 16, 31, 85 and 137) were highly immunogenic. No significant differences in antibody responses were found between HIV infected participants (n = 40) and uninfected donors (n = 40) for 6 out of the 8 epitopes tested. The antibody response against nucleocapsid (peptide 137) was significantly lower (p < 0.001), and the response to QP1 (peptide 157) significantly higher (p < 0.05) in HIV-infected adults compared to uninfected individuals. Among those with HIV infection, the level of response against p15 protein (peptide 85) was significantly lower in untreated individuals controlling HIV (“elite” controllers) compared to untreated non-controllers (p < 0.05) and uninfected donors (p < 0.05). In contrast, the response against the capsid protein (epitopes 81 and 117) was significantly higher in controllers compared to uninfected donors (p < 0.001 and <0.05 respectively) and non-controllers (p < 0.01 and <0.05). Peripheral blood mononuclear cells (PBMCs) from study participants were tested for responses against HERV-K (HML-2) capsid recombinant peptide in gamma interferon (IFN-γ) enzyme immunospot (Elispot) assays. We found that the HERV-K (HML-2) Gag antibody and T cell response by Elispot were significantly correlated. HIV elite controllers had a strong cellular and antibody response against HERV-K (HML-2) Gag directed mainly against the Capsid region. Collectively, these data suggest that anti-HERV-K (HML-2) antibodies targeting capsid could have an immunoprotective effect in HIV infection. The online version of this article (doi:10.1186/s12977-017-0365-2) contains supplementary material, which is available to authorized users.
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