Fate of the inner nuclear membrane protein lamin B receptor and nuclear lamins in herpes simplex virus type 1 infection

During herpesvirus egress, capsids bud through the inner nuclear membrane. Underlying this membrane is the nuclear lamina, a meshwork of intermediate filaments with which it is tightly associated. Details of alterations to th e lamina and the inner nuclear membrane during infection and the mechanisms involved in capsid transport across these structures remain unclear. Here we describe the fate of key protein components of the nuclear envelope and lamina during herpes simplex virus type 1 (HSV-1) infection. We followed th e distribution of the inner nuclear membrane protein lamin B receptor (LBR) and Iamins A and B-2 tagged with green fluorescent protein (GFP) in live i nfected cells. Together with additional results from indirect immunofluores cence, our studies reveal major morphologic distortion of nuclear-rim LBR a nd lamins A/C, B-1 and B-2. By 8 h p.i., we also observed a significant red istribution of LBR-GFP to the endoplasmic reticulum, where it colocalized w ith a subpopulation of cytoplasmic glycoprotein B by immunofluorescence. In addition, analysis by fluorescence recovery after photobleaching reveals t hat LBR-GFP exhibited increased diffusional mobility within the nuclear mem brane of infected cells. This is consistent with the disruption of interact ions between LBR and the underlying lamina. In addition to studying stably expressed GFP-lamins by fluorescence microscopy, we studied endogenous A- a nd B-type lamins in infected cells by Western blotting. Both approaches rev eal a loss of Iamins associated with virus infection. These data indicate m ajor disruption of the nuclear envelope and lamina of HSV-1-infected cells and are consistent with a virus-induced dismantling of the nuclear lamina, possibly in order to gain access to the inner nuclear membrane.