title: Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency.
abstract: Using nonsense and deletion mutants of herpes simplex virus type 1, we investigated the roles of three immediate-early proteins (ICP4, ICP27 and ICP0) in the establishment and reactivation of ganglionic latency in a mouse ocular model. DNA hybridization, superinfection-rescue, and cocultivation techniques provided quantitative data that distinguished between the failure of a virus to establish latency in the ganglion and its failure to reactivate. Null mutants with lesions in the genes for ICP4 and ICP27 did not replicate in the eye or in ganglia and failed to establish reactivatable latent infections. Three ICP0 deletion mutants which could replicate in the eye and ganglia varied in their ability to establish and reactivate from the latent state, demonstrating that ICP0 plays a role both in the establishment and the reactivation of latency. The use of viral mutants and a variety of stage-specific assays allowed us to better define the stages in the establishment and reactivation of herpes simplex virus type 1 latency.
authors.affiliation: Laboratory of Tumor Virus Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: D A
authors.initials: DA
authors.lastname: Leib
authors.forename: D M
authors.initials: DM
authors.lastname: Coen
authors.forename: C L
authors.initials: CL
authors.lastname: Bogard
authors.forename: K A
authors.initials: KA
authors.lastname: Hicks
authors.forename: D R
authors.initials: DR
authors.lastname: Yager
authors.forename: D M
authors.initials: DM
authors.lastname: Knipe
authors.forename: K L
authors.initials: KL
authors.lastname: Tyler
authors.forename: P A
authors.initials: PA
authors.lastname: Schaffer
mesh_terms: D000818:Animals; D005123:Eye; D005814:Genes, Viral; D051379:Mice; D018139:Simplexvirus / Q000235:genetics* / Q000502:physiology; D012668:Trigeminal Ganglion; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D014764:Viral Proteins