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H. Ghiasi, Y. Osorio, K. Asotra, S. Lapoint, F. Hofman; Ocular Infection of BALB/c Mice With a Recombinant HSV-1 Expressing Murine IL-2 Cause CNS Demyelination and Chronic CNS Infection . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4185.
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Purpose:To determine if combination of viral infection in the brain and continuous expression of IL-2 produce hind limb weakness and CNS demyelination in infected mice. Methods:Female BALB/c mice were infected ocularly with HSV-1 recombinant viruses expressing IL-2, IL-4, and IFN-gamma. Wt McKrae, KOS, and parental viruses were used as controls. Demyelination in brain and spinal cord of infected mice was determined by light microscopy and EM from 7 to 75 days post infection. Infiltration into the brains and spinal cords of CD4+, CD8+, CD62L, CD45RB, macrophages, HSV-1, IL-2, and IL-12 were monitored by immunocytochemistry and FACS analysis. In addition, presence of infectious virus in CNS of infected mice was measured by confucal microscopy and RT-PCR. Results:Histological examination of mice infected with HSV-IL-2 revealed that demyelination lesions were found in periventicular white matter, brain stem, and spinal cord white matter. Physical examination of infected mice showed transient hind limb weakness and/or paralysis. In contrast, mouse infected with HSV-IL-4, HSV-IFN-gamma, or control viruses did not exhibit such phenotypes. In addition, HSV-IL-2 infected mice showed a chronic rather than a latent infection in their CNS. Finally, HSV-IL-2 infected mice had a significant elevation of T cells and macrophages in their CNS compared with control viruses. Conclusions:We suggest that the combination of viral infection and IL-2 expression in the brain leads to recruitment of both T cells and macrophages into the CNS. This cellular accumulation could lead to demyelination, with the macrophages exacerbating the process by expressing IL-12 and pushing the immune response toward a TH1 response. This study outlines for the first time a novel mouse model to study CNS demyelination that utilizes both a viral and an immune component.
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