Optic neuritis in different strains of mice by a recombinant HSV-1 expressing murine interleukin-2.
OBJECTIVE
The authors have shown previously that a recombinant HSV-1 that constitutively expresses two copies of murine IL-2 (HSV-IL-2) induces demyelination by activated CD8(+) T cells in the brain and spinal cord of ocularly infected female BALB/c mice. The present study was conducted to determine whether the ocular infection with this recombinant virus induces optic neuritis independent of virus dose, major histocompatibility complex (MHC) background, or sex.


METHODS
Female BALB/c, C57BL/6, SJL/6, and 129SVE mice and male BALB/c mice were ocularly infected with different doses of recombinant HSV-IL-2 virus. Demyelination of optic nerves in infected mice was monitored histologically using Luxol fast blue staining and by measurement of visual-evoked cortical potentials (VECPs).


RESULTS
Both focal and diffuse regions of demyelination of the optic nerves were observed in the HSV-IL-2-infected mice as early as day 10 after infection and as late as day 60 after infection (the final experimental time point) in all strains of mice tested. Optic nerve demyelination was not observed in control mice ocularly infected with HSV-IL-4 or wild-type HSV-1. VECP responses were delayed significantly in the HSV-IL-2-infected mice compared with mice infected with control viruses.


CONCLUSIONS
The results demonstrate for the first time that a combination of viral infection and constitutive expression of IL-2, but not IFN-gamma or IL-4, can result in demyelination and visual impairment in the optic nerves of ocularly infected mice.
Zandian
Mandana
M
Department of Surgery, Cedars-Sinai Burns and Allen Research Institute, Center for Neurobiology and Vaccine Development, Los Angeles, California, USA.
Belisle
Raelene
R
Mott
Kevin R
KR
Nusinowitz
Steven
S
Hofman
Florence M
FM
Ghiasi
Homayon
H
D000818:Animals; D004396:Coloring Agents / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual / Q000502:physiology*; D015828:Eye Infections, Viral / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007211:Indoles / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009902:Optic Neuritis / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D014793:Visual Cortex / Q000503:physiopathology
D004396:Coloring Agents; D007211:Indoles; D007376:Interleukin-2; C018588:Luxol Fast Blue MBS