Timing Is Everything

N. Drayman et al. in their recent article (mBio 8:e01612-17, 2017, https://doi.org/10.1128/mBio.01612-17) have used dynamic proteomics and machine learning to show that the cell cycle state of any individual cell affects the outcome of a productive herpes simplex virus 1 (HSV-1) infection. Cells infected from early G₁ through S were most permissive for expression of genes from the HSV-1 genome, whereas cells infected in late G₂ to mitosis were much less so. Most of the infected cells that underwent mitosis became permanently nonpermissive for HSV-1 gene expression afterward. The cell cycle stage accounted for 60% of the success of infection, and cell density and motility accounted for most of the rest. To successfully reactivate, HSV-1 must express its genes in neurons and cells of the spinosum and granulosum epidermis strata. These cells are permanently in the cell cycle stages most permissive for HSV-1 gene expression, and none reenters mitosis, thus maximizing the efficiency of a successful HSV-1 reactivation before the adaptive immunity can control it.