Farías Mónica A, Cancino Felipe A, Navarro Areli J, Duarte Luisa F, Soto Abel A, Tognarelli Eduardo I, Ramm Maximiliano J, Alarcón-Zapata Bárbara N, Cordero José, San Martín Sergio, Agurto-Muñoz Cristian, Retamal-Díaz Angello, Riedel Claudia A, Barrera Nelson P, Bustamante Luis, Bueno Susan M, Kalergis Alexis M, González Pablo A
Millennium Institute on Immunology and Immunotherapy, Chile.
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
iScience. 2025 Apr 15;28(5):112441. doi: 10.1016/j.isci.2025.112441. eCollection 2025 May 16.
Herpes simplex virus type 1 (HSV-1) significantly impairs dendritic cell (DC) function, ultimately eliciting the death of these cells. Here, we sought to assess whether HSV-1 modulates lipid metabolism in mouse DCs as a mechanism of immune evasion. For this, we performed RT-qPCR gene arrays with ingenuity pathway analysis (IPA), RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA), confocal microscopy, transmission electron microscopy, ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) analysis, pharmacological inhibition of eight lipid-metabolism-related enzymes in HSV-1-infected DCs, co-cultures between virus-specific transgenic CD4 and CD8 T cells and HSV-1-infected DCs, and assays with mice. We found that HSV-1 significantly alters lipid metabolism in DCs and induces lipid droplet (LD) accumulation in these cells. Pharmacological inhibition of two particular lipid metabolism enzymes was found to partially restore DC function. Overall, these results suggest that lipid metabolism plays an important role in the impairment of DC function by HSV-1.
1型单纯疱疹病毒（HSV-1）会显著损害树突状细胞（DC）的功能，最终导致这些细胞死亡。在此，我们试图评估HSV-1是否通过调节小鼠DC中的脂质代谢作为一种免疫逃逸机制。为此，我们进行了带有 Ingenuity 通路分析（IPA）的逆转录定量聚合酶链反应（RT-qPCR）基因芯片、RNA测序（RNA-seq）和基因集富集分析（GSEA）、共聚焦显微镜检查、透射电子显微镜检查、超高效液相色谱-四极杆飞行时间（UHPLC-QTOF）分析、对HSV-1感染的DC中八种脂质代谢相关酶的药理学抑制、病毒特异性转基因CD4和CD8 T细胞与HSV-1感染的DC之间的共培养以及对小鼠的实验。我们发现HSV-1会显著改变DC中的脂质代谢，并诱导这些细胞中脂滴（LD）的积累。发现对两种特定脂质代谢酶的药理学抑制可部分恢复DC功能。总体而言，这些结果表明脂质代谢在HSV-1对DC功能的损害中起重要作用。
