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同时感染HIV和SARS-CoV-2的住院患者的血浆蛋白质组学分析

Plasma proteomic profiling of hospitalized patients co-infected with HIV and SARS-CoV-2.

作者信息

Zhang Xinyu, Yan Xuan, Sun Jinfeng, Shao Yueming, Song Wei, Qi Tangkai, Wang Zhenyan, Tang Yang, Sun Jianjun, Xun Jingna, Song Zichen, Xu Shuibao, Yang Junyang, Wang Jiangrong, Chen Jun, Zhang Renfang, Liu Li, Shen Yinzhong

机构信息

Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.

出版信息

Front Immunol. 2025 Jun 11;16:1601672. doi: 10.3389/fimmu.2025.1601672. eCollection 2025.

Abstract

BACKGROUND

The interaction between human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections presents a critical challenge to immunopathogenesis. While HIV infection induces progressive CD4 T cell depletion and chronic immune dysfunction, SARS-CoV-2 triggers complex host responses, ranging from localized antiviral defense to systemic hyperinflammation. We aimed to illustrate the plasma proteomic profiles of hospitalized patients coinfected with HIV and SARS-CoV-2.

METHODS

Liquid chromatography-tandem mass spectrometry was used to analyze the plasma protein profiles in three matched groups: (1) seven hospitalized patients with HIV and SARS-CoV-2 coinfection, (2) seven people living with HIV (PLWH) who tested negative for SARS-CoV-2, and (3) seven healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the differentially expressed proteins (DEPs).

RESULTS

We quantified 5,373 proteins across 21 samples and identified significant alterations in multiple proteins in people living with HIV (PLWH) with COVID-19 compared to both PLWH and healthy controls. These DEPs were associated with inflammatory responses, immune cell migration, degranulation, and, notably, the complement and coagulation cascades. In addition, we identified DEPs associated with SARS-CoV-2 infection, including viral receptors, proteases, transcription factors, and kinases.

CONCLUSIONS

The proteomic profile highlighted the disruption caused by COVID-19 in immunomodulation, thrombosis, and viral entry pathways in PLWH. Further validation of these signatures could improve risk stratification and tailored interventions for this vulnerable patient cohort.

摘要

背景

人类免疫缺陷病毒(HIV)与严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染之间的相互作用对免疫发病机制构成了严峻挑战。HIV感染会导致CD4 T细胞逐渐耗竭和慢性免疫功能障碍,而SARS-CoV-2会引发复杂的宿主反应,从局部抗病毒防御到全身炎症反应。我们旨在阐明HIV和SARS-CoV-2合并感染的住院患者的血浆蛋白质组学特征。

方法

采用液相色谱-串联质谱法分析三个匹配组的血浆蛋白质谱:(1)七名HIV和SARS-CoV-2合并感染的住院患者,(2)七名SARS-CoV-2检测呈阴性的HIV感染者(PLWH),以及(3)七名健康对照者。对差异表达蛋白(DEP)进行基因本体论和京都基因与基因组百科全书富集分析。

结果

我们对21个样本中的5373种蛋白质进行了定量分析,发现与PLWH和健康对照者相比,感染COVID-19的PLWH中有多种蛋白质发生了显著变化。这些DEP与炎症反应、免疫细胞迁移、脱颗粒,尤其是补体和凝血级联反应有关。此外,我们还鉴定出了与SARS-CoV-2感染相关的DEP,包括病毒受体、蛋白酶、转录因子和激酶。

结论

蛋白质组学特征突出了COVID-19对PLWH免疫调节、血栓形成和病毒进入途径造成的破坏。对这些特征的进一步验证可以改善这一脆弱患者群体的风险分层和针对性干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c52/12187658/d1dae69d92ad/fimmu-16-1601672-g001.jpg

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