Outcome of bovine herpesvirus 4 infection following direct viral injection in the lateral ventricle of the mouse brain

Microbes Infect. 2006 Mar;8(3):898-904. doi: 10.1016/j.micinf.2005.10.016. Epub 2006 Feb 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytopathogenic Effect, Viral
  • Gene Expression Regulation, Viral
  • Herpesviridae Infections / virology*
  • Herpesvirus 4, Bovine / metabolism*
  • Immediate-Early Proteins / metabolism
  • Lateral Ventricles / virology*
  • Male
  • Mice
  • Trans-Activators / metabolism
  • Tumor Virus Infections / virology*


  • IE2 protein, bovine herpesvirus type 4
  • Immediate-Early Proteins
  • Trans-Activators