Simian virus 40 induces lamin A/C fluctuations and nuclear envelope deformation during cell entry.

In non-dividing cells, the nuclear pore complex provides the major route for viruses and viral genomes to enter the nucleus. However, SV40 infection of non-dividing cells is very inefficient suggesting that the nuclear envelope prevents most viral genomes from entering the nucleus. Surprisingly, we observed that following infection of quiescent CV-1 cells with SV40, the nuclear envelope was dramatically deformed, as seen by immunohistochemistry detection of lamins A/C, B1, B2 and the nuclear pore complexes. Accompanying deformation of the nuclear envelope, we also observed fluctuations in the levels of lamin A/C, dephosphorylation of an unknown epitope on lamin A/C and accumulation of lamin A in the cytoplasm. The nuclear envelope deformations occured just prior to and during nuclear entry of the viral genome and were transient and the spherical structure of the nuclear envelope was restored subsequent to nuclear entry. Nuclear envelope deformation and lamin A/C dephosphorylation required caspase-6 cleavage of a small fraction of lamin A/C. Taken together the results suggest that virus-induced alterations of the nuclear lamina, are involved in the nuclear entry of the SV40 genome in non-dividing cells. We propose that SV40 utilize this unique, previously unknown mechanism for direct trafficking of its genome from the ER to the nucleus.