Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina.
Replication of human cytomegalovirus is limited at the level of nucleocytoplasmic transport of viral capsids, a process that requires the disassembly of the nuclear lamina. Deletion of the protein kinase gene UL97 from the viral genome showed that the activity of pUL97 plays an important role for viral capsid egress. Here, we report that p32, a novel cellular interactor of the viral kinase pUL97, promotes the accumulation of pUL97 at the nuclear membrane by recruiting the p32-pUL97 complex to the lamin B receptor. Transfection of active pUL97, but not a catalytically inactive mutant, induced a redistribution of lamina components as demonstrated for recombinant lamin B receptor-green fluorescent protein and endogenous lamins A and C. Consistent with this, p32 itself and lamins were phosphorylated by pUL97. Importantly, overexpression of p32 in human cytomegalovirus-infected cells resulted in increased efficiency of viral replication and release of viral particles. Thus, it is highly suggestive that the cellular protein p32 recruits pUL97 to induce a dissolution of the nuclear lamina thereby facilitating the nuclear export of viral capsids.
Marschall
Manfred
M
Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Erlangen 91054, Germany. manfred.marschall@viro.ned.uni-erlangen.de
Marzi
Andrea
A
aus dem Siepen
Patricia
P
Jochmann
Ramona
R
Kalmer
Martina
M
Auerochs
Sabrina
S
Lischka
Peter
P
Leis
Martina
M
Stamminger
Thomas
T
D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002999:Clone Cells; D003587:Cytomegalovirus / Q000201:enzymology* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D034881:Nuclear Lamina / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D020798:Two-Hybrid System Techniques; D014779:Virus Replication
C087299:C1QBP protein, human; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D049452:Green Fluorescent Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase