Calcium-signal facilitates herpes simplex virus type 1 nuclear transport through slingshot 1 and calpain-1 activation

• HSV-1 entry activates intracellular calcium signal.
• PLCγ1 and IP3R-1 are required for HSV-1-induced calcium signal.
• SSH and calpain-1 are activated by calcium signal.
• SSH and calpain-1 facilitate HSV-1 nuclear transport.

Herpes simplex virus type 1 (HSV-1) can establish its latency in neurons and is associated with virus-induced pathological neurodegeneration in the nervous system. Here we show that viral penetration-induced calcium release facilitated HSV-1 intracellular trafficking through activating slingshot 1 (SSH), a phosphatase regulating actin filament dynamics. More detailed studies revealed that phospholipase C gamma 1, and the inositol 1,4,5-trisphosphate receptor isoform 1 were required for SSH activation. Besides, calpain-1, a calcium-dependent cysteine protease, was involved in viral intracellular migration. These results may lead to new targets for antiviral therapy.