Regulated Nuclear Localization of the Varicella-zoster Virus Major Regulatory Protein, IE62

The major transcriptional regulatory protein encoded by varicella-zoster virus (VZV), IE62, accumulates within the nucleus of transfected and VZV-infected cells. Data are presented to show that nuclear localization of IE62 is dependent upon charged amino acids mapping to residues 677-685 of the 1310 residue protein. Furthermore, coexpression of VZV open-reading frame (ORF) 66 with IE62 results in the accumulation of cytoplasmic forms of IE62, suggesting that the ORF 66 protein can override the IE62 nuclear localization signal. Consistent with this, cytoplasmic forms of IE62 were detected in VZV-infected cells at late but not immediate early times after infection. The ORF 66 protein, a putative protein kinase, did not affect nuclear localization of other proteins, and IE62 nuclear localization was not affected by coexpression with VZV ORF 47, another putative kinase. These results suggest that IE62 nuclear functions may be specifically regulated by the VZV ORF 66 protein.