Apoptosis in Acute and Chronic Central Nervous System Disease Induced by Theiler's Murine Encephalomyelitis Virus

Abstract

Apoptosis has been observed in neural development and in various neurological diseases, including viral infection and multiple sclerosis. Theiler's murine encephalomyelitis virus is divided into two subgroups based on neurovirulence: the highly neurovirulent GDVII strain produces an acute fatal polioencephalomyelitis in mice, whereas the attenuated DA strain produces demyelination with virus persistence preceded by an acute infection. TUNEL combined with immunocytochemistry was used to detect apoptosis in the central nervous system and to characterize which cell types were involved during the acute stage in both GDVII and DA virus infection and during the chronic stage in DA virus infection. We found that during the acute stage, apoptosis was induced in neurons in both virus infections. However, the number of apoptotic neurons was much greater in GDVII virus-infected mice than in DA virus-infected mice (P < 0.01). During the chronic stage of DA virus infection, apoptotic cells were detected only in the spinal cord white matter. Some of these cells were dual labeled for fragmented DNA and carbonic anhydrase II, an oligodendrocyte marker. Our results indicate that apoptosis of neurons could be responsible for the fatal outcome in GDVII virus infection. In contrast, apoptosis of oligodendrocytes can contribute to the chronic demyelinating DA virus infection.

Apoptotic and Antiapoptotic Activity of L Protein of Theiler's Murine Encephalomyelitis Virus

“…This form of cell death has been of interest with respect to TMEV because of the marked difference in virulence and persistence manifested by strains of the two subgroups of TMEV: GDVII and other members of the GDVII subgroup are highly virulent, causing a fatal acute disease with no virus persistence, while DA, BeAn, and other members of the TO subgroup cause a chronic, progressive demyelinating disease in which virus routinely persists in the CNS for the life of the mouse. Apoptosis has been reported both in the acute disease caused by DA and GDVII virus and during chronic TMEV-IDD (2,5,20,26). A number of different cell types have been found to undergo apoptosis, including activated macrophages/microglia, T cells, and oligodendrocytes.…”

“…During TMEV-IDD, apoptosis of T cells, microglia/macrophages, and oligodendrocytes has been described (2,5,20,26). In vitro studies have implicated the cardiovirus L protein, which is encoded between the start of the polyprotein and the P1 capsid proteins (Fig.…”

TGF-β1 suppresses T cell infiltration and VP2 puff B mutation enhances apoptosis in acute polioencephalitis induced by Theiler's virus

“…Four-micrometer-thick sections were stained with Luxol fast blue. Apoptosis was detected using the TUNEL method (Tsunoda et al, 1997). TUNEL + cells were visualized by the avidin-biotin peroxidase complex (ABC) technique (Vector, Burlingame, CA) with 3, 3′-diaminobenzidine tetrahydrochloride (DAB, Sigma) as chromogen.…”

“…One week after infection of SJL/J mice with GDVII, DA, DApB or DApBL2M virus, we compared the extent of apoptotic cells in the brains of infected-mice, using TUNEL staining (Tsunoda et al, 1997). Apoptotic neurons were prominent in the brains of mice infected with GDVII virus (Fig.…”

“…*Correspondence to: Robert S. Fujinami, Ph.D., Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, Utah 84132,During the acute phase, GDVII and DA viruses cause distinct neuropathology. Like other picornaviruses, such as poliovirus (Gosselin et al, 2003;López-Guerrero et al, 2000), both GDVII and DA viruses induce apoptosis (Tsunoda et al, 1997). Infection of mice with GDVII virus causes apoptosis in relatively high numbers of neurons in the CNS.…”