Endogenous gamma interferon produced in central nervous system by systemic infection infection with Theiler's virus in mice

Abstract

Theiler's virus GD VII strain causes acute encephalomyelitis by intracerebral inoculation. We established acute encephalomyelitis in mice by the intravenous (i.v.) inoculation of Theiler's virus GD VII strain. Replication of Theiler's virus injected i.v. could be observed in both the brain and spinal cord of mice, and interferon (IFN)-gamma could be detected in the extracts of brain and spinal cord in parallel with viral replication. Furthermore, by the injection of anti-IFN-gamma monoclonal antibody (mAb) on Day 1 post-infection (p.i.), mortality and virus titres in the spinal cord increased compared with the control mice treated with normal rat globulin. The histological exacerbation of inflammation was observed in spinal cord of anti-IFN-gamma mAb-treated mice. These results indicate that endogenous IFN-gamma, produced locally in the brain and spinal cord of mice through both antiviral action and anti-inflammatory action of IFN-gamma in central nervous system, plays an important role in Theiler's virus infection.

Paralysis caused by acute myelitis in Theiler's murine encephalomyelitis virus strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal cord

“…On the other hand, some of these mice that received immunosuppressive treatment and died, showed severe wasting and tetraplegia for a short time before death. In GD VII strain infection, encephalitis precedes myelitis (Kohanawa et al, 1993) and the elimination of the virus from the brain is dependent on T lymphocytes (Kohanawa et al, 1994). Therefore, some of the mice that die might be paralysed because of the deterioration due to encephalitis, and this paralysis would be caused by lyric infection.…”

“…route, viral replication and elimination are observed in the central nervous system (CNS) and the infected mice show paralysis until day 20 post-infection (p.i.) (Kohanawa et al, 1993). Histological inflammatory findings and the infectious virus disappear in the CNS of the infected mice after day 30 p.i.…”

“…The resulting tissue homogenates were frozen and thawed twice and clarified by centrifugation at 500 g for 30 rain. The virus in the supernatant of the tissue homogenate was quantified by plaque assay of BHK-21 ceils (Kohanawa et al, 1993).…”

Theiler's virus is eliminated by a gamma-interferon-independent mechanism in the brain

“…In our observation on Theiler's virus GD VII strain, endogenous interferon gamma (IFN-y) was produced in the brains and spinal cords of the infected mice (Kohanawa et al, 1993). IFN-T which is secreted by natural killer (NK) cells and T lymphocytes (Klavinskis et al, 1989;Taylor et al, 1989;Nakane et al, 1991) is an important cytokine in viral infections (Klavinskis et al, 1989;Leist et al, 1989;Smith et al, 1991;Lucin et al, 1992).…”

“…For a 50% lethal dose of GD VII strain injected intravenously (i.v.) and having a count of 1.4 x 108 PFU/mouse, the infected mice show symptoms of wasting and paralysis, and the elimination of the virus from CNS tissues was observed (Kohanawa et al, 1993). The mechanisms on the elimination of GD VII strain virus from CNS tissues have not been elucidated.…”