Outcome of bovine herpesvirus 4 infection following direct viral injection in the lateral ventricle of the mouse brain.
A recombinant bovine herpesvirus 4 (BoHV-4EGFPDeltaTK), obtained by the insertion of an EGFP gene into the TK locus of DN 599 BoHV-4 strain, was injected into the lateral ventricle of the brain of mice and a clinical score was evaluated for 90 days. Although BoHV-4 was not neuro-pathogenic, BoHV-4EGFPDeltaTK transduction capability was analyzed. EGFP expression was localized in close proximity to the border of the ventricles and EGFP-positive cells were found to co-localize with ependymal cells. Although most of the cells had a polarized morphology, they were not neurons. EGFP-positive cells were seen to spread in tangentially oriented rows within the rostral migratory stream (RMS). Co-localization of EGFP signal with anti-GFAP antibody showed that they were glial cells. EGFP-positive cells were observed until 31 days post-injection and then disappeared completely. Virus isolation was possible at an early post-injection time (3 days), but then virus titer was below the detection limits at later times. Viral DNA, however, could be detected until 21 days post-injection. Thus, in this report we showed that (i) BoHV-4EGFPDeltaTK did not replicate in the mouse brain, (ii) is not pathogenic and (iii) gene transfer can be obtained in long-lived cells belonging to the RMS after BoHV-4EGFPDeltaTK injection within the lateral ventricle.
Donofrio
Gaetano
G
Dipartimento di Salute Animale, Sezione di Malattie Infettive degli Animali, Università di Parma, Via del Taglio 8, 43100 Parma, Italy. gaetano.donofrio@unipr.it
Cavaggioni
Andrea
A
Bondi
Michela
M
Cavirani
Sandro
S
Flammini
Cesidio Filippo
CF
Mucignat-Caretta
Carla
C
D000818:Animals; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000821:virology*; D026021:Herpesvirus 4, Bovine / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000821:virology*; D008297:Male; D051379:Mice; D015534:Trans-Activators / Q000378:metabolism; D014412:Tumor Virus Infections / Q000821:virology*
C079185:IE2 protein, bovine herpesvirus type 4; D017874:Immediate-Early Proteins; D015534:Trans-Activators