ICP4-Associated Activation of Rap1b Facilitates Herpes Simplex Virus Type I (HSV-1) Infection in Human Corneal Epithelial Cells

The strong contribution of RAS-related protein 1b (Rap1b) to cytoskeleton remodeling determines intracellular and extracellular physiological activities, including the successful infection viruses in permissive cells, but its role HSV-1 life cycle is still unclear. Here, we demonstrated that immediate early (IE) gene ICP4 inhibits kinase A (PKA) phosphorylation induce Rap1b-activation-mediated viral infection. Rap1b activation membrane enrichment begin at stage remain active during proliferation period virus. Treating cells with small interfering RNA (siRNA) showed a dose-dependent decrease levels, no increase was observed after overexpression. Further investigation indicated suppression derives from phosphorylated PKA mutants partial or complete prenylation instead phosphorylation, which promoted manner. Furthermore, agonist Forskolin disturbed manner, accompanied by decreasing trend Moreover, IE induced dephosphorylation, leading continuous activation, followed rearrangement cell division control 42 (CDC42) Ras-related C3 botulinum toxin substrate 1 (RAC1). These further stimulated membrane-triggered processes favoring virus Altogether, show significance uncover mechanism determined posttranslational regulation host protein.