Translocation and colocalization of ICP4 and ICP0 in cells infected with herpes simplex virus 1 mutants lacking glycoprotein E, glycoprotein I, or the virion host shutoff product of the UL41 gene.
In wild-type herpes simplex virus 1-infected cells, the major regulatory protein ICP4 resides in the nucleus whereas ICP0 becomes dynamically associated with proteasomes and late in infection is translocated and dispersed in the cytoplasm. Inhibition of proteasomal function results in retention or transport of ICP0 to the nucleus. We report that in cells infected with mutants lacking glycoprotein E (gE), glycoprotein I (gI), or the product of the U(L)41 gene, both ICP4 and ICP0 are translocated to the cytoplasm and coaggregate in small dense structures that, in the presence of proteasomal inhibitor MG132, also contain proteasomal components. Gold particle-conjugated antibody to ICP0 reacted in thin sections with dense protein aggregates in the cytoplasm of mutant virus-infected cells. Similar aggregates were present in the nuclei but not in the cytoplasm of wild-type virus-infected cells. Exposure of cells early in infection to MG132 does not result in retention of ICP0 as in wild-type virus-infected cells. The results suggest that the retention of ICP4 and ICP0 in the nucleus is a dynamic process that involves the function of other viral proteins that may include the Fc receptor formed by the gE/gI complex and is not merely the consequence of expression of a nuclear localization signal. It is noteworthy that in DeltaU(L)41-infected cells gE is retained in the trans-Golgi network and is not widely dispersed in cellular membranes.
Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, 910 East 58th Street, Chicago, IL 60637, USA.
Maria
M
Kalamvoki
Jianguo
J
Qu
Bernard
B
Roizman
D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D003593:Cytoplasm / Q000737:chemistry / Q000648:ultrastructure / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000378:metabolism*; D009154:Mutation; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics*; D014771:Virion / Q000235:genetics / Q000378:metabolism; D021601:trans-Golgi Network / Q000737:chemistry / Q000378:metabolism
D017874:Immediate-Early Proteins; C081688:Ul41 protein, Human herpesvirus 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C044768:glycoprotein E, herpes simplex virus type 1; C064959:glycoprotein I, herpes simplex virus type 1; C048925:herpes simplex virus, type 1 protein ICP4; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1