Multiomics profiling of plasma reveals lipid-immune dysregulation and exosome remodeling in mpox and mpox-HIV co-infection.

IF 13.3 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2026-09-11 Epub Date: 2026-08-19 DOI:10.1016/j.medj.2026.101264

Siqi Yong, Jiaying Zhang, He Tian, Zehua Wang, Shaohua Zhang, Robin Barry Chan, Yingjuan Zhou, Guibin Wang, Lianchun Liang, Zhifeng Song, Jingwen Han, Gaofeng Ma, Sin Man Lam, Yingmei Feng, Guanghou Shui

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引用次数: 0

Abstract

Background: Monkeypox virus (MPXV) infects diverse human cell types, and human immunodeficiency virus (HIV) co-infection is common. The immunometabolic consequences of MPXV infection, and how it may be altered by HIV, remain poorly defined.

Methods: We performed quantitative plasma lipidomics and precise metabolomics in a discovery cohort (n = 81) comprising MPXV-monoinfected (MPLWOH), MPXV-HIV-coinfected (MPLWH), and HIV-monoinfected (PLWH) patients and healthy controls, integrating exosome proteomics, cytokine profiling, and transcriptomics of exosome-treated HepG2 and A549 cells for functional interpretation. An independent validation cohort (n = 65) was used to assess cross-cohort reproducibility.

Findings: MPXV infection induced broad lipid remodeling, with elevations in phosphatidylserine (PS) and phosphatidylethanolamine (PE) and reductions in phosphatidylcholine (PC), lysophospholipids, cholesteryl ester (CE), and exosomal lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). These lipid alterations were correlated with tissue injury markers and inflammatory cytokines. The MPLWH group exhibited more severe metabolic disruption, including marked sulfatide (SL) depletion, lower cholesterol and high-density lipoprotein cholesterol (HDL-c), and extensive rewiring of lipid-cytokine associations. SL depletion in MPLWH correlated with abundances of COPI-mediated retrograde trafficking proteins in exosomes. Transcriptomic profiling of exosome-treated cells provided functional validation: MPLWOH exosomes induced lipid metabolism and repair-associated epithelial programs, while MPLWH exosomes drove phospholipid remodeling and acute inflammatory and mucosal barrier-stress responses.

Conclusions: MPXV infection reprograms host lipid metabolism and exosome composition, with HIV co-infection amplifying inflammatory, metabolic, and trafficking disruptions. These convergent multi-omics signatures link systemic lipid dysregulation to exosome-mediated immunomodulation and identify potential targets for host-directed interventions.

Funding: This study was funded by the Major Project of Guangzhou National Laboratory.

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血浆多组学分析揭示了m痘和m痘- hiv合并感染中的脂质免疫失调和外泌体重塑。

背景：猴痘病毒（MPXV）感染多种人类细胞类型，人类免疫缺陷病毒（HIV）合并感染是常见的。MPXV感染的免疫代谢后果，以及它如何被HIV改变，仍然没有明确的定义。方法：我们在包括mpxv -单感染（MPLWOH）、mpxv - hiv -共感染（MPLWH）和hiv -单感染（PLWH）患者和健康对照的发现队列（n = 81）中进行了定量血浆脂质组学和精确代谢组学，整合了外泌体蛋白质组学、细胞因子谱和外泌体处理的HepG2和A549细胞的转录组学，以进行功能解释。采用独立验证队列（n = 65）评估跨队列的可重复性。结果：MPXV感染引起广泛的脂质重塑，磷脂酰丝氨酸（PS）和磷脂酰乙醇胺（PE）升高，磷脂酰胆碱（PC）、溶血磷脂、胆固醇酯（CE）和外泌体卵磷脂-胆固醇酰基转移酶（LCAT）和脂蛋白脂肪酶（LPL）降低。这些脂质改变与组织损伤标志物和炎症细胞因子相关。MPLWH组表现出更严重的代谢紊乱，包括显著的硫脂（SL）消耗、更低的胆固醇和高密度脂蛋白胆固醇（HDL-c），以及脂质-细胞因子关联的广泛重新布线。MPLWH中SL的缺失与外泌体中copi介导的逆行运输蛋白的丰度相关。外泌体处理细胞的转录组学分析提供了功能验证：MPLWOH外泌体诱导脂质代谢和修复相关的上皮程序，而MPLWH外泌体驱动磷脂重塑和急性炎症和粘膜屏障应激反应。结论：MPXV感染重编程宿主脂质代谢和外泌体组成，HIV合并感染放大炎症、代谢和运输中断。这些趋同的多组学特征将全身脂质失调与外泌体介导的免疫调节联系起来，并确定了宿主定向干预的潜在目标。经费：本研究由广州国家实验室重大项目资助。

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

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

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