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.
Institute for Clinical and Molecular Virology, University of Erlangen-Nürnberg, Erlangen 91054, Germany. manfred.marschall@viro.ned.uni-erlangen.de
Manfred
M
Marschall
Andrea
A
Marzi
Patricia
P
aus dem Siepen
Ramona
R
Jochmann
Martina
M
Kalmer
Sabrina
S
Auerochs
Peter
P
Lischka
Martina
M
Leis
Thomas
T
Stamminger
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