Abstract
Abstract: :
Purpose: Cellular structure is vastly altered by most lytic viral infections, including the herpesvirus VZV, the cause of herpes zoster and many subsequent problems affecting vision. The VZV gene 66 protein kinase prevents nuclear import of a viral regulatory protein, IE62, a protein key to infection, and thus the kinase has antiviral potential. Examination of this interaction spawned the possibility that the kinase also affects the host cell. In the search for host cell targets, we examined the actin cytoskeleton in cells expressing this protein kinase Methods: Vero, HFF and MeWo cells (permissive for VZV infection) were examined for phalloidin stained actin stress fibers by immunofluorescence following transfection with plasmids expressing gene 66, or infection with adenoviruses expressing gene 66 kinase, or with VZV. Results: A major fraction of cells expressing the VZV gene 66 protein kinase, following either plasmid transfection or infection with adenoviruses, demonstrated partial or complete disorganization and breakdown of phalloidin stained stress fibers. This was not found in control transfections or adenoviral infections. Actin accumulated in the cytoplasm in disorganized compartments. Actin stress fibers were also found to be disorganized in late stage VZV infected cells. Conclusions: The effect of the gene 66 protein kinase on cellular stress fibers is strong evidence of host cell targets of the protein kinase in addition to the viral target regulatory protein IE62. Homologs of VZV66 are in all alphaherpesviruses and all target similar motifs; Actin dissorganization has also been observed for the homologous US3 protein kinases in HSV and PRV. This suggests a common cellular target or pathway for these kinases.
Keywords: varicella zoster virus • herpes simplex virus • cytoskeleton