Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States.
Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, CA, United States; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, CA, United States.
Photodiagnosis Photodyn Ther. 2024 Jun;47:104097. doi: 10.1016/j.pdpdt.2024.104097. Epub 2024 Apr 26.
Under controlled settings, narrow-band ultraviolet A (UVA) exposure exerts antiviral effects both in vivo and in vitro. The effect is thought to be mediated via direct effect on viral particles and indirectly, by modulation of metabolic pathways of host cells. We aimed to explore the extracellular and intracellular antiviral effects of UVA exposure against Alpha, Beta, and Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Vero E6 kidney normal epithelial cells and human tracheal epithelial cells were infected with Alpha, Beta, and Delta variants in a BSL-3 laboratory. To assess extracellular effects, SARS-CoV-2 variants were directly exposed to a single dose of UVA prior to infection of the host cells (Vero E6 kidney normal epithelial cells and human tracheal epithelial cells) The intracellular effects of UVA were assessed by first infecting the cells with SARS-CoV-2 variants followed by UVA treatment of infected cell monolayers. Efficacy was quantified by both plaque reduction assay and quantitative real-time polymerase chain reaction. Additionally, transcriptomic analysis was performed on exposed Vero E6 cells to assess differentially expressed genes and canonical pathways as compared to controls.
SARS-CoV-2 Alpha, Beta and Delta variants are susceptible to UVA exposure prior to infection of Vero E6 cells. Importantly, the UVA-driven reduction in Delta variant load could be reproduced in human primary tracheal cells. Beta and Delta variants load also significantly decreased during Vero E6 cells intracellular experiments. UVA-driven reductions in viral loads ameliorate several host metabolic pathways, including canonical pathways related to viral infection and interferon signaling.
Narrow-band UVA exhibits both extracellular effects on SARS-CoV-2 viral particles and intracellular effects on infected cells with SARS-CoV-2. Efficacy appears to be variant independent.
在受控环境下，窄谱紫外线 A（UVA）照射对 SARS-CoV-2 的 Alpha、Beta 和 Delta 变体具有体内和体外的抗病毒作用。这种作用被认为是通过对病毒颗粒的直接作用以及对宿主细胞代谢途径的间接调节来介导的。我们旨在探索 UVA 照射对 SARS-CoV-2 Alpha、Beta 和 Delta 变体的细胞外和细胞内抗病毒作用。
在 BSL-3 实验室中，将 Vero E6 肾脏正常上皮细胞和人气管上皮细胞感染 Alpha、Beta 和 Delta 变体。为了评估细胞外作用，在感染宿主细胞（Vero E6 肾脏正常上皮细胞和人气管上皮细胞）之前，SARS-CoV-2 变体直接暴露于单次剂量的 UVA 下。通过先感染细胞，然后用 UVA 处理感染细胞单层，评估 UVA 的细胞内作用。通过噬斑减少测定和定量实时聚合酶链反应来定量评估功效。此外，对暴露的 Vero E6 细胞进行转录组分析，以评估与对照相比差异表达的基因和经典途径。
SARS-CoV-2 Alpha、Beta 和 Delta 变体在感染 Vero E6 细胞之前易受 UVA 照射。重要的是，UVA 驱动的 Delta 变体载量减少可以在人原代气管细胞中重现。Beta 和 Delta 变体载量在 Vero E6 细胞内实验过程中也显著降低。UVA 驱动的病毒载量降低可改善多种宿主代谢途径，包括与病毒感染和干扰素信号相关的经典途径。
窄谱 UVA 对 SARS-CoV-2 病毒颗粒具有细胞外作用，对感染 SARS-CoV-2 的细胞具有细胞内作用。功效似乎与变体无关。
