Hofmann Katharina, Hofmann Samuel, Weigl Franziska, Mai Julia, Schreiner Sabrina
Institute of Virology, School of Medicine, Technical University of Munich, 80333 München, Germany.
Tissue Bank of the German Center for Infection Research (DZIF), Partner Site Heidelberg, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Viruses. 2024 Apr 19;16(4):633. doi: 10.3390/v16040633.
Differentiated HepaRG cells are popular in vitro cell models for hepatotoxicity studies. Their differentiation is usually supported by the addition of dimethyl sulfoxide (DMSO), an amphipathic solvent widely used in biomedicine, for example, in potential novel therapeutic drugs and cryopreservation of oocytes. Recent studies have demonstrated drastic effects, especially on epigenetics and extracellular matrix composition, induced by DMSO, making its postulated inert character doubtful. In this work, the influence of DMSO and DMSO-mediated modulation of differentiation on human adenovirus (HAdV) infection of HepaRG cells was investigated. We observed an increase in infectivity of HepaRG cells by HAdVs in the presence of 1% DMSO. However, this effect was dependent on the type of medium used for cell cultivation, as cells in William's E medium showed significantly stronger effects compared with those cultivated in DMEM. Using different DMSO concentrations, we proved that the impact of DMSO on infectability was dose-dependent. Infection of cells with a replication-deficient HAdV type demonstrated that the mode of action of DMSO was based on viral entry rather than on viral replication. Taken together, these results highlight the strong influence of the used cell-culture medium on the performed experiments as well as the impact of DMSO on infectivity of HepaRG cells by HAdVs. As this solvent is widely used in cell culture, those effects must be considered, especially in screening of new antiviral compounds.
分化的HepaRG细胞是用于肝毒性研究的常用体外细胞模型。它们的分化通常通过添加二甲基亚砜（DMSO）来支持，DMSO是一种广泛应用于生物医学的两亲性溶剂，例如用于潜在的新型治疗药物和卵母细胞的冷冻保存。最近的研究表明，DMSO会产生显著影响，尤其是对表观遗传学和细胞外基质组成的影响，这使得其假定的惰性特征受到质疑。在这项工作中，研究了DMSO及其介导的分化调节对人腺病毒（HAdV）感染HepaRG细胞的影响。我们观察到在1% DMSO存在下，HAdV对HepaRG细胞的感染性增加。然而，这种效应取决于用于细胞培养的培养基类型，因为与在DMEM中培养的细胞相比，在William's E培养基中的细胞显示出明显更强的效应。使用不同浓度的DMSO，我们证明了DMSO对感染性的影响是剂量依赖性的。用复制缺陷型HAdV感染细胞表明，DMSO的作用模式基于病毒进入而非病毒复制。综上所述，这些结果突出了所用细胞培养基对所进行实验的强烈影响以及DMSO对HAdV感染HepaRG细胞感染性的影响。由于这种溶剂在细胞培养中广泛使用，必须考虑这些影响，尤其是在筛选新的抗病毒化合物时。
