title: The herpes simplex virus 2 UL21 protein is essential for virus propagation.
abstract: Herpes simplex virus 2 (HSV-2) is an important human pathogen that is the major cause of genital herpes infections and a significant contributor to the epidemic spread of human immunodeficiency virus infections. The UL21 gene is conserved throughout the Alphaherpesvirinae subfamily and encodes a tegument protein that is dispensable for HSV-1 and pseudorabies virus replication in cultured cells; however, its precise functions have not been determined. To investigate the role of UL21 in the HSV-2 replicative cycle, we constructed a UL21 deletion virus (HSV-2 ΔUL21) using an HSV-2 bacterial artificial chromosome, pYEbac373. HSV-2 ΔUL21 was unable to direct the production of infectious virus in noncomplementing cells, whereas the repaired HSV-2 ΔUL21 strain grew to wild-type (WT) titers, indicating that UL21 is essential for virus propagation. Cells infected with HSV-2 ΔUL21 demonstrated a 2-h delay in the kinetics of immediate early viral gene expression. However, this delay in gene expression was not responsible for the inability of cells infected with HSV-2 ΔUL21 to produce virus insofar as late viral gene products accumulated to WT levels by 24 h postinfection (hpi). Electron and fluorescence microscopy studies indicated that DNA-containing capsids formed in the nuclei of ΔUL21-infected cells, while significantly reduced numbers of capsids were located in the cytoplasm late in infection. Taken together, these data indicate that HSV-2 UL21 has an early function that facilitates viral gene expression as well as a late essential function that promotes the egress of capsids from the nucleus.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Le Sage
authors.forename: Masany
authors.initials: M
authors.lastname: Jung
authors.forename: Jake D
authors.initials: JD
authors.lastname: Alter
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Wills
authors.forename: Susan M
authors.initials: SM
authors.lastname: Johnston
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Joel D
authors.initials: JD
authors.lastname: Baines
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Banfield
mesh_terms: D000818:Animals; D002213:Capsid / Q000737:chemistry / Q000648:ultrastructure; D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology; D022202:Chromosomes, Artificial, Bacterial; D003593:Cytoplasm / Q000821:virology; D017353:Gene Deletion; D020043:Genes, Essential; D005816:Genetic Complementation Test; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000502:physiology*; D050296:Microbial Viability; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins