title: Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo.
abstract: There remains a lack of agreement on the effect of antiviral therapy on herpes simplex virus (HSV) latency and subsequent reactivation. To gain insight into this important issue, a single-cell polymerase chain reaction assay was used to quantify the effects of high-dose acyclovir on latent infection in a mouse model. Treatment with 50 mg/kg of acyclovir every 8 h reduced the number of latently infected neurons by >90% when treatment was begun before 24 h after infection and by 80% and 70% when begun at 48 or 72 h after infection, respectively. The biologic significance of these reductions was evaluated by using a well-established in vivo reactivation model. The number of animals in which virus reactivated was reduced significantly, even when acyclovir therapy was delayed until 72 h after infection, a time when animals had developed lesions. These findings indicate that potent antiviral therapy during early primary HSV infection can reduce the magnitude of the latent infection, such that a significant decrease in reactivation is observed.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. Sawtn0@chmcc.org
authors.forename: N M
authors.initials: NM
authors.lastname: Sawtell
authors.forename: R L
authors.initials: RL
authors.lastname: Thompson
authors.forename: L R
authors.initials: LR
authors.lastname: Stanberry
authors.forename: D I
authors.initials: DI
authors.lastname: Bernstein
mesh_terms: D000208:Acute Disease; D000212:Acyclovir / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D005123:Eye / Q000821:virology; D006561:Herpes Simplex / Q000188:drug therapy* / Q000503:physiopathology; D018259:Herpesvirus 1, Human; D051379:Mice; D009474:Neurons / Q000821:virology*; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000821:virology; D014775:Virus Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir