title: The weakly virulent herpes simplex virus type 1 strain KOS-63 establishes peripheral and central nervous system latency following intranasal infection of rabbits, but poorly reactivates in vivo.
abstract: The virological, clinical and electrophysiological manifestations of acute and experimentally reactivated infections of the rabbit central nervous system (CNS) and trigeminal ganglia have been studied after intranasal infection with herpes simplex virus type 1 (strain KOS-63). All animals shed virus in nasal secretions during the acute phase of infection. Although no rabbits developed clinical signs during the acute phase of infection, mild electroencephalographic (EEG) abnormalities consistent with viral invasion of the CNS were seen. KOS-63 produced only occasional gross and histopathologic herpetic lesions of the CNS and was very rarely recovered from the brain. These results indicate that KOS-63 was poorly neuroinvasive and only mildly neurovirulent during the acute phase of infection. However, KOS-63 did establish latency within the CNS and trigeminal ganglia of infected rabbits as demonstrated by in situ hybridization and by recovery of virus from co-cultivation cultures, but not from cell-free homogenates of nervous tissue. Cyclophosphamide and dexamethasone injections were used to reactivate latent CNS and trigeminal ganglionic infections. Following injection of the drugs, no animal shed virus in nasal secretions or developed obvious clinical or EEG changes. However, KOS-63 was recovered from co-cultivation cultures of brain and trigeminal ganglia at greater frequency following drug injection than during latency. These results indicate that KOS-63 was only poorly susceptible to drug-induced reactivation. In vivo experiments confirmed that the apparent poor neuroinvasiveness and weak neurovirulence of KOS-63 was not due to viral temperature-sensitive defects, deficient production of viral thymidine kinase, or abnormal defects in viral DNA polymerase function.
authors.affiliation: Department of Veterans Affairs Medical Center Ophthalmology Research Laboratory, Houston, Texas.
authors.forename: W G
authors.initials: WG
authors.lastname: Stroop
authors.forename: M C
authors.initials: MC
authors.lastname: Banks
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000382:microbiology* / Q000473:pathology; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004569:Electroencephalography; D006561:Herpes Simplex / Q000382:microbiology* / Q000473:pathology; D009296:Nasal Cavity / Q000378:metabolism / Q000382:microbiology*; D009693:Nucleic Acid Hybridization; D010525:Peripheral Nerves / Q000382:microbiology* / Q000473:pathology; D011817:Rabbits; D018139:Simplexvirus / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D013696:Temperature; D013937:Thymidine Kinase / Q000378:metabolism; D014775:Virus Activation
chemical_list: D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase