Spheroids Based on Human Embryonic Lung Cell Line (HELC-3) and Their Use for the Accumulation of Herpes Simplex Virus Type 1

Traditional two-dimensional (2D) cell cultures have limited capabilities for modeling complex interactions between viruses and host cells, which reduces the efficiency of the studies when trying to transfer data obtained to in vivo models. Three-dimensional (3D) cell cultures are the most physiologically relevant models, without the limitations inherent to 2D cultures. The use of 3D models opens up new possibilities when studying viral infections and developing new antiviral drugs and preventive measures. We constructed a biological model based on 3D spheroids from the human embryonic lung cell line (HELC-3) and tested it on the example of the analysis of replicative activity of herpes simplex virus type 1, strain L2 (HSV-1/L2). The spheroids were obtained when cultivating the cells in hydrogel microwells. The replicative activity of HSV-1 in 3D culture of HELC-3 cells was estimated by a cytopathic effect of the culture liquid of virus-infected spheroids on a monolayer culture of the same cells (2D format). It was demonstrated that HSV-1 replicates efficiently in spheroids. Thus, the model based on 3D spheroids from HELC-3 cells can be considered as a promising tool for studying the HSV-1 replication cycle in vitro, molecular mechanisms of its pathogenesis and persistence, as well as the analysis of potential antiviral drugs and vaccines.