title: Differences in pathogenicity of herpes simplex virus serotypes 1 and 2 may be observed by histopathology and high-resolution magnetic resonance imaging in a murine encephalitis model.
abstract: The mouse model for herpes simplex-induced encephalitis (HSE) is an established preclinical tool for evaluating the efficacy of new therapeutic interventions. We evaluated the utility of high-resolution in vivo MRI in observing the progression of experimental HSE during the first week postinfection. Female BALB/c mice were inoculated intracerebrally with HSV-1 or HSV-2 by microinjection. Each animal was evaluated daily by high-resolution (4.7 Tesla) T(2) weighted MRI and clinical disease scoring (neurological and behavioral). Lesions induced by a high dose of HSV-1 (1000 PFU) were detectable by MRI without administration of contrast agent whereas for low dose HSV-1 (100 PFU), administration of contrast agent was necessary to visualize the lesions in the brain. The correlation between the MRI and histologic results was excellent. No HSV-2 induced lesions were observed by MRI. Although both HSV serotypes caused similar clinical disease, significant type differences were found by histologic and MRI examinations. HSV-1 caused necrotizing meningoencephalitis, whereas HSV-2 induced mostly meningitis. The data indicate that in vivo high-resolution MRI may be useful to longitudinally evaluate HSV-1-related pathology in a mouse model of HSE and potentially could be used for monitoring the efficacy of anti-infective therapeutic approaches.
authors.affiliation: Department of Safety Assessment, SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania 19426, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Thomas
authors.forename: R D
authors.initials: RD
authors.lastname: Kapadia
authors.forename: G I
authors.initials: GI
authors.lastname: Wells
authors.forename: A M
authors.initials: AM
authors.lastname: Gresham
authors.forename: D
authors.initials: D
authors.lastname: Sutton
authors.forename: H A
authors.initials: HA
authors.lastname: Solleveld
authors.forename: S K
authors.initials: SK
authors.lastname: Sarkar
authors.forename: S B
authors.initials: SB
authors.lastname: Dillon
authors.forename: R
authors.initials: R
authors.lastname: Tal-Singer
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000473:pathology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D018258:Herpesvirus 2, Human / Q000472:pathogenicity*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D014774:Virulence