Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection.
Herpes simplex virus 1 (HSV-1) replicates in the nucleus of host cells and radically alters nuclear architecture as part of its replication process. Replication compartments (RCs) form, and host chromatin is marginalized. Chromatin is later dispersed, and RCs spread past it to reach the nuclear edge. Using a lamin A-green fluorescent protein fusion, we provide direct evidence that the nuclear lamina is disrupted during HSV-1 infection and that the UL31 and UL34 proteins are required for this. We show nuclear expansion from 8 h to 24 h postinfection and place chromatin rearrangement and disruption of the lamina in the context of this global change in nuclear architecture. We show HSV-1-induced disruption of the localization of Cdc14B, a cellular protein and component of a putative nucleoskeleton. We also show that UL31 and UL34 are required for nuclear expansion. Studies with inhibitors of globular actin (G-actin) indicate that G-actin plays an essential role in nuclear expansion and chromatin dispersal but not in lamina alterations induced by HSV-1 infection. From analyses of HSV infections under various conditions, we conclude that nuclear expansion and chromatin dispersal are dispensable for optimal replication, while lamina rearrangement is associated with efficient replication.
Simpson-Holley
Martha
M
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, 02115, USA.
Colgrove
Robert C
RC
Nalepa
Grzegorz
G
Harper
J Wade
JW
Knipe
David M
DM
D000199:Actins / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D054637:Dual-Specificity Phosphatases; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D034881:Nuclear Lamina / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013997:Time Factors; D014764:Viral Proteins / Q000502:physiology; D014779:Virus Replication
D000199:Actins; D002843:Chromatin; D009687:Nuclear Proteins; C108721:UL31 protein, Human herpesvirus 1; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins; C474200:CDC14B protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases