title: Herpes simplex virus 1 pUL34 plays a critical role in cell-to-cell spread of virus in addition to its role in virus replication.
abstract: Herpes simplex virus (HSV) pUL34 plays a critical role in virus replication by mediating egress of nucleocapsids from the infected cell nucleus. We have identified a mutation in pUL34 (Y68A) that produces a major defect in virus replication and impaired nuclear egress but also profoundly inhibits cell-to-cell spread and trafficking of gE. Virion release to the extracellular medium is not affected by the Y68A mutation, indicating that the mutation specifically inhibits cell-to-cell spread. We isolated extragenic suppressors of the Y68A plaque formation defect and mapped them by a combination of high-throughput Illumina sequencing and PCR-based screening. We found that suppression is highly correlated with a nonsense mutation in the US9 gene, which plays a critical role in cell-to-cell spread of HSV-1 in neurons. The US9 mutation alone is not sufficient to suppress the Y68A spread phenotype, indicating a likely role for multiple viral factors.
authors.affiliation: Department of Microbiology, The University of Iowa, 3-432 Bowen Science Building, Iowa City, IA 52242, USA.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Haugo
authors.forename: Moriah L
authors.initials: ML
authors.lastname: Szpara
authors.forename: Lance
authors.initials: L
authors.lastname: Parsons
authors.forename: Lynn W
authors.initials: LW
authors.lastname: Enquist
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roller
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D017931:DNA Primers; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins