Abstract
ABSTRACTN. 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.
Highlights
Drayman et al [2] have experimentally tested whether the state of the individual cell plays a significant role in determining the outcome of an herpes simplex virus 1 (HSV-1) infection. They first screened a library of cell clones, each expressing a different green fluorescent protein (GFP)-tagged full-length protein from its endogenous locus, by tracking the progression of the infection using a reporter cyan fluorescent protein (CFP) expressed from the HSV-1 genome
Using machine learning to detect the time from last mitosis, Drayman and colleagues directly tested whether the cell cycle stage at which a cell is infected determines the outcome of the infection
HSV-1 gene expression was high in cells infected anytime from immediately after mitosis until approximately 14 h later and decreased in cells infected until 22 h after the previous mitosis, suggesting that cells are broadly permissive until late G2
Summary
Commentary the cell cycle stage of the infected cells was important for the establishment of a productive HSV-1 infection [3]. Using machine learning to detect the time from last mitosis, Drayman and colleagues directly tested whether the cell cycle stage at which a cell is infected determines the outcome of the infection.
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