Significance of host cell kinases in herpes simplex virus type 1 egress and lamin-associated protein disassembly from the nuclear lamina.
The nuclear lamina is thought to be a steric barrier to the herpesvirus capsid. Disruption of the lamina accompanied by phosphorylation of lamina proteins is a conserved feature of herpesvirus infection. In HSV-1-infected cells, protein kinase C (PKC) alpha and delta isoforms are recruited to the nuclear membrane and PKC delta has been implicated in phosphorylation of emerin and lamin B. We tested two critical hypotheses about the mechanism and significance of lamina disruption. First, we show that chemical inhibition of all PKC isoforms reduced viral growth five-fold and inhibited capsid egress from the nucleus. However, specific inhibition of either conventional PKCs or PKC delta does not inhibit viral growth. Second, we show hyperphosphorylation of emerin by viral and cellular kinases is required for its disassociation from the lamina. These data support hypothesis that phosphorylation of lamina components mediates lamina disruption during HSV nuclear egress.
Leach
Natalie R
NR
Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242, USA.
Roller
Richard J
RJ
D000818:Animals; D001483:Base Sequence; D002213:Capsid / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D034881:Nuclear Lamina / Q000187:drug effects / Q000201:enzymology / Q000821:virology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014709:Vero Cells; D019065:Virus Assembly / Q000187:drug effects / Q000502:physiology; D057074:Virus Release / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D017931:DNA Primers; D008565:Membrane Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; C092710:emerin; D011493:Protein Kinase C