title: A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1.
abstract: Herpes simplex virus (HSV) persists in the human population by establishing long-term latent infections followed by periodic reactivation and transmission. Latent infection of sensory neurons is characterized by repression of viral productive-cycle gene expression, with abundant transcription limited to a single locus that encodes the latency-associated transcripts (LATs). We have observed that LAT- deletion mutant viruses express viral productive-cycle genes in greater numbers of murine trigeminal ganglion neurons than LAT+ HSV type 1 at early times during acute infection but show reduced reactivation from latent infection. Thus, a viral function associated with the LAT region exerts an effect at an early stage of neuronal infection to reduce productive-cycle viral gene expression. These results provide the first evidence that the virus plays an active role in down-regulating productive infection during acute infection of sensory neurons. The effect of down-regulation of productive-cycle gene expression during acute infection may contribute to viral evasion from the host immune responses and to reduced cytopathic effects, thereby facilitating neuronal survival and the establishment of latency.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Garber
authors.forename: P A
authors.initials: PA
authors.lastname: Schaffer
authors.forename: D M
authors.initials: DM
authors.lastname: Knipe
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D012333:RNA, Messenger / Q000502:physiology*; D012367:RNA, Viral / Q000032:analysis; D012668:Trigeminal Ganglion / Q000821:virology*; D014709:Vero Cells; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral