Central Nervous System Demyelination in Herpes Simplex Virus Type 2 Infection
The pathogenesis of primary and reactivated herpes simplex virus type 2 (HSV-2) infection is examined in mice to determine its nervous system effects and its potential for causing demyelination. In intracerebrally and vaginally infected mice, there is a broad spectrum of possible disease outcomes. A mainly demyelinative CNS pathology is the consequence of non-fatal infections, while animals with fatal infectious have non-selective, severe infection and disease of both the gray and white matter. The mechanism of demyelination involves the infection and loss of oligodendrocytes, but whether this is a purely cytolytic infectious process is unclear. Elongated spinal cord demyelinative lesions which appear to be tract associated, and presence of virus in axons in acute demyelinative lesions suggest a model of virus spread from neurons to the cells that myelinate their axons, with amplification of infection in the white matter. In the genital infection model, antibody responses may appear late or be undetected, thymic cortical necrosis tends to segregate with severe infection, and the capacity to isolate virus from lymphoid tissues is restricted to animals with fatal infections, raising the possibility that at virus-induced immunosuppression may be a determinant of severe infections. In a model of viral latency established by a genital route in which 50% or more of mice develop small demyelinative cord lesions during primary infections, HSV-2 reactivations were successfully induced in many mice using immunosuppressive treatment. With reactivation, virus could be isolated from the vagina and CNS. Antigen was found in T9-L2 and L6-S2 ganglia, with lesser amounts in distal roots and in the spinal cord; recurrent CNS demyelinative lesions were not found. The potential importance of these findings in understanding human HSV-2 infection and demyelinative disease is discussed.
KeywordsFatal Infection Demyelinative Lesion Neutralize Antibody Response Gray Matter Lesion Central Nervous System Demyelination
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