Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity.
Studies of human cytomegalovirus (HCMV) UL97 kinase deletion mutant (DeltaUL97) indicated a multi-step role for this kinase in early and late phases of the viral life cycle, namely, in DNA replication, capsid maturation and nuclear egress. Here, we addressed its possible involvement in cytoplasmic steps of HCMV assembly. Using the DeltaUL97 and the UL97 kinase inhibitor NGIC-I, we demonstrate that the absence of UL97 kinase activity results in a modified subcellular distribution of the viral structural protein assembly sites, from compact structures impacting upon the nucleus to diffuse perinuclear structures punctuated by large vacuoles. Infection by either wild type or DeltaUL97 viruses induced a profound reorganization of wheat germ agglutinin (WGA)-positive Golgi-related structures. Importantly, the viral-induced Golgi remodeling along with the reorganization of the nuclear architecture was substantially altered in the absence of UL97 kinase activity. These findings suggest that UL97 kinase activity might contribute to organization of the viral cytoplasmic assembly sites.
Azzeh
Maysa
M
Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, Jerusalem, Israel 91120.
Honigman
Alik
A
Taraboulos
Albert
A
Rouvinski
Alexander
A
Wolf
Dana G
DG
D002462:Cell Membrane / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry / Q000821:virology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D003593:Cytoplasm / Q000737:chemistry / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D017353:Gene Deletion; D006056:Golgi Apparatus / Q000821:virology; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology*; D013347:Subcellular Fractions / Q000737:chemistry; D014617:Vacuoles / Q000737:chemistry / Q000821:virology; D019065:Virus Assembly / Q000235:genetics
D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase