Schematic representation of spatial translational activity during plaque progression.

(A) Current view anticipated from present data. Infection initiating at the focal centre of infection (red circle) radiates outward (red arrow), with naïve uninfected cells at the extreme perimeter. Immediately adjacent internal cells represent the earliest/most recently infected cells and progressively more central cells represent the progressively later/“older” infected cells. Absolute translation levels are indicated in green with declining levels indicated by increasing grey. A cross-sectional slice (arrowed line) indicating relative overall levels from peripheral to central cells, is summarised in the graph below, where the x-axis indicates space from external to internal and therefore time from new to old. (B) A revised model shows distinct regionalisation of overall translational activity, with early pronounced suppression at the periphery together with restoration of translational levels in the more interior cells. (C) Model of an extended regional shutoff zone due to translational suppression in an increased numbers of cells as discussed in the text. (D) Spatial representation of translational activity in HaCaT cells during early progression (left scheme), where no apparent advanced shutoff zone is observed and later progression (right scheme) where uninfected naïve cells become progressively more susceptible and advanced shutoff operates.