Cell type-specific differences in herpes simplex virus type 1 infection and dependency on ICP27

While many cell types are permissive to herpes simplex virus type 1 (HSV-1) infection, the efficiency and outcome of infection can vary significantly depending on the cell type infected. In addition, viral mutants may replicate more favorably in one cell type compared to another. Here, we sought to identify key differences in the infectious cycle of HSV-1 and infection in the absence of infected cell protein 27 (ICP27) in several cell types used for HSV-1 research. These include African green monkey kidney epithelial (Vero), human lung fibroblast (MRC-5), human foreskin fibroblast (HFF), human diploid keratinocyte (N/TERT-2G), and human cervical cancer epithelial (HeLa) cells. ICP27 is an essential viral immediate early gene product that promotes efficient processing and transport of viral mRNAs. Based on previous studies, replication of an ICP27 mutant virus is cell type-dependent. Here, we demonstrate that the kinetics of wild-type infection, including the timing of the onset of viral DNA replication, mRNA and protein expression, and infectious virus output, are also cell type-dependent. We also found that while infection with an ICP27 deletion mutant leads to a decrease in viral mRNA and protein expression in all cell types tested, some cell types are more reliant on ICP27 for viral DNA replication. Together, this study highlights cell type-specific differences in HSV-1 infection and underscores the importance of cellular context in determining the efficiency of infection and reliance on ICP27.IMPORTANCEHSV-1 research has been completed in multiple cell types, which have inherently different characteristics. This study analyzes the nuclear stages of HSV-1 infection in multiple cell types commonly used in HSV-1 research. We illustrate the cell type specificity of HSV-1 infection with respect to viral DNA replication, mRNA expression, protein expression, infectious virus output, and the effect a viral mutation has on these processes. These data reveal significant differences in infection depending on the cell type infected and could serve as a resource for future HSV-1 research. This study also underscores potential limitations when comparing data collected across different cell types, as results may be cell type-specific.