title: VP16 serine 375 is a critical determinant of herpes simplex virus exit from latency in vivo.
abstract: Development of novel prevention and treatment strategies for herpes simplex virus (HSV) mediated diseases is dependent upon an accurate understanding of the central molecular events underlying the regulation of latency and reactivation. We have recently shown that the transactivation function of the virion protein VP16 is a critical determinant in the exit from latency in vivo. HSV-1 strain SJO2 carries a single serine to alanine substitution at position 375 in VP16 which disrupts its interaction with its essential co-activator Oct-1. Here we report that SJO2 is severely impaired in its ability to exit latency in vivo. This result reinforces our prior observations with VP16 transactivation mutant, in1814, in which VP16 interaction with Oct-1 is also disrupted and solidifies the importance of the VP16-Oct-1 interaction in the early steps in HSV-1 reactivation.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. nancy.sawtell@cchmc.org
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Sawtell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Triezenberg
authors.forename: Richard L
authors.initials: RL
authors.lastname: Thompson
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000821:virology*; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011984:Sensory Receptor Cells / Q000821:virology; D012694:Serine / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014775:Virus Activation / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics
chemical_list: D017405:Herpes Simplex Virus Protein Vmw65; D050811:Octamer Transcription Factor-1; D012694:Serine