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HIV 进展者和精英控制者血浆酰基辅酶 A 结合蛋白 (ACBP)浓度的差异。

Distinct Plasma Concentrations of Acyl-CoA-Binding Protein (ACBP) in HIV Progressors and Elite Controllers.

机构信息

Infectious Disease and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H4A 4J1, Canada.

Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC H4A 4J1, Canada.

出版信息

Viruses. 2022 Feb 23;14(3):453. doi: 10.3390/v14030453.

Abstract

HIV elite controllers (ECs) are characterized by the spontaneous control of viral replication, and by metabolic and autophagic profiles which favor anti-HIV CD4 and CD8 T-cell responses. Extracellular acyl coenzyme A binding protein (ACBP) acts as a feedback inhibitor of autophagy. Herein, we assessed the circulating ACBP levels in ECs, compared to people living with HIV (PLWH) receiving antiretroviral therapy (ART) or not. We found lower ACBP levels in ECs compared to ART-naïve or ART-treated PLWH (p < 0.01 for both comparisons), independently of age and sex. ACBP levels were similar in ECs and HIV-uninfected controls. The expression of the protective HLA alleles HLA-B*27, *57, or *58 did not influence ACBP levels in ECs. ACBP levels were not associated with CD4 or CD8 T-cell counts, CD4 loss over time, inflammatory cytokines, or anti-CMV IgG titers in ECs. In ART-treated PLWH, ACBP levels were correlated with interleukin (IL)-1β levels, but not with other inflammatory cytokines such as IL-6, IL-8, IL-32, or TNF-α. In conclusion, ECs are characterized by low ACBP plasma levels compared to ART-naïve or ART-treated PLWH. As autophagy is key to anti-HIV CD4 and CD8 T-cell responses, the ACBP pathway constitutes an interesting target in HIV cure strategies.

摘要

HIV 精英控制器 (ECs) 的特点是病毒复制的自发控制,以及有利于抗 HIV CD4 和 CD8 T 细胞反应的代谢和自噬谱。细胞外酰基辅酶 A 结合蛋白 (ACBP) 作为自噬的反馈抑制剂。在此,我们评估了 ECs 中的循环 ACBP 水平,并与接受抗逆转录病毒治疗 (ART) 的 HIV 感染者 (PLWH) 或未接受治疗的患者进行了比较。我们发现,与未经 ART 治疗或接受 ART 治疗的 PLWH 相比,ECs 中的 ACBP 水平较低 (两种比较均 p < 0.01),与年龄和性别无关。ECs 中的 ACBP 水平与 HIV 未感染者相似。保护性 HLA 等位基因 HLA-B*27、*57 或 *58 的表达并不影响 ECs 中的 ACBP 水平。ACBP 水平与 ECs 中的 CD4 或 CD8 T 细胞计数、随时间推移的 CD4 丢失、炎症细胞因子或抗 CMV IgG 滴度无关。在接受 ART 治疗的 PLWH 中,ACBP 水平与白细胞介素 (IL)-1β 水平相关,但与其他炎症细胞因子如 IL-6、IL-8、IL-32 或 TNF-α无关。总之,与未经 ART 治疗或接受 ART 治疗的 PLWH 相比,ECs 的 ACBP 血浆水平较低。由于自噬是抗 HIV CD4 和 CD8 T 细胞反应的关键,因此 ACBP 途径是 HIV 治愈策略中的一个有趣靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0485/8949460/4fa5f26b41a1/viruses-14-00453-g001.jpg

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