SARS-CoV-2 structural proteins affect the expression of IL-8 and TNF-α cytokines and APOBEC genes in human lung A549 and liver Huh-7 cells.

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI:10.2478/acph-2025-0024
Martina Bergant Marušič, Margarida Costa, Špela Turk, Nika Lovšin
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引用次数: 0

Abstract

The apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) proteins belong to a family of cytidine deami nases responsible for DNA and RNA sequence editing, playing pivotal roles in a wide range of biological processes, including immune responses, antiviral properties, and genetic mutations. In this work, we investigated the effect of SARS-CoV-2 structural proteins - Envelope (E), Spike (S), Nucleocapsid (N), Membrane (M) and protein ORF6 - on the expression of cytokines Interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-α), and APOBEC3s proteins (APOBEC3B and APOBEC3F) genes in Huh-7 and A549 human cell lines. While there is plenty of scientific evidence about the effects of SARS-CoV-2 on the inflammatory cascade, the current literature regarding the impact of SARS-CoV-2 on APOBEC expression is scarce. Our findings reveal a complex relationship between SARS-CoV-2 structural proteins and the host immune response, as certain viral structural proteins (S, M, E) modulate cytokine expression, potentially contributing to the dysregulated immune responses seen in COVID-19 patients. Additionally, our research uncovered interactions between viral proteins and APOBEC genes. This study contributes to a better understanding of the host-virus interactions in the context of SARS-CoV-2 infection and provides some insights into potential therapeutic targets for mitigating the immunopathological consequences of the disease.

SARS-CoV-2结构蛋白影响人肺A549和肝Huh-7细胞中IL-8、TNF-α细胞因子和APOBEC基因的表达
载脂蛋白B mRNA编辑催化多肽样(APOBEC)蛋白属于胞苷类酶家族,负责DNA和RNA序列编辑,在广泛的生物过程中发挥关键作用,包括免疫反应、抗病毒特性和基因突变。在这项工作中,我们研究了SARS-CoV-2结构蛋白-包膜(E)、刺突(S)、核衣壳(N)、膜(M)和蛋白ORF6 -对人类Huh-7和A549细胞系中白细胞介素8 (IL-8)和肿瘤坏死因子α (TNF-α)以及APOBEC3s蛋白(APOBEC3B和APOBEC3F)基因表达的影响。虽然有大量的科学证据表明SARS-CoV-2对炎症级联反应的影响,但目前关于SARS-CoV-2对APOBEC表达影响的文献很少。我们的研究结果揭示了SARS-CoV-2结构蛋白与宿主免疫反应之间的复杂关系,因为某些病毒结构蛋白(S, M, E)调节细胞因子的表达,可能导致COVID-19患者的免疫反应失调。此外,我们的研究发现了病毒蛋白和APOBEC基因之间的相互作用。本研究有助于更好地了解SARS-CoV-2感染背景下的宿主-病毒相互作用,并为减轻该疾病免疫病理后果的潜在治疗靶点提供一些见解。
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来源期刊
Acta Pharmaceutica
Acta Pharmaceutica PHARMACOLOGY & PHARMACY-
CiteScore
5.20
自引率
3.60%
发文量
20
审稿时长
>12 weeks
期刊介绍: AP is an international, multidisciplinary journal devoted to pharmaceutical and allied sciences and contains articles predominantly on core biomedical and health subjects. The aim of AP is to increase the impact of pharmaceutical research in academia, industry and laboratories. With strong emphasis on quality and originality, AP publishes reports from the discovery of a drug up to clinical practice. Topics covered are: analytics, biochemistry, biopharmaceutics, biotechnology, cell biology, cell cultures, clinical pharmacy, drug design, drug delivery, drug disposition, drug stability, gene technology, medicine (including diagnostics and therapy), medicinal chemistry, metabolism, molecular modeling, pharmacology (clinical and animal), peptide and protein chemistry, pharmacognosy, pharmacoepidemiology, pharmacoeconomics, pharmacodynamics and pharmacokinetics, protein design, radiopharmaceuticals, and toxicology.
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