|[Frontiers in Bioscience 1, d241-247, September 1, 1996]|
HERPES SIMPLEX VIRUS: A TOOL FOR NEUROSCIENTISTS
Frank J. Jenkins1 and Sharon L. Turner2
1 Department of Pathology, School of Medicine; 1Department of
Infectious Diseases and Microbiology, School of Public Health;
Received 08/02/96; Accepted 08/08/96; On-line 09/01/96
Animal studies have demonstrated that during an acute infection, HSV spreads from peripheral epithelial cells to both the peripheral nervous system (PNS) and central nervous system (CNS; 13-17). Interestingly, cellular damage induced by the virus is markedly different between the PNS and CNS. Tissue damage in the PNS is generally mild while the damage in the CNS is often extensive within a local foci. A well studied example of this concept is seen within the trigeminal root entry zone (TREZ) of the brainstem, a junction region between the PNS and CNS (13, 14, 18). Within this region, following an acute HSV infection, the peripheral myelin is untouched while the CNS side of the trigeminal root develops demyelinated lesions. Within the demyelinated lesions, there is an absence of myelin and the presence of both intact axons and a mononuclear cell (MNC) infiltrate. The exact mechanism of demyelination is not known, but the results from several studies suggest that it is a combination of cellular infection and host immune response.
Glucocorticoid-induced immunosuppression has been reported to reduce immune cell infiltrate and myelin destruction in the CNS portion of the TREZ following peripheral HSV infection (14) and demyelinating lesions were absent in nude (athymic) mice inoculated corneally with HSV (19). A recent study comparing TREZ demyelination following peripheral HSV infection in immunocompetent mice, immune deficient mice, and immunocompetent mice immunosuppressed with glucocorticoids, demonstrated that immune deficient or immunosuppressed mice exhibited reduced levels or no demyelinating lesions (20). These studies demonstrate the role of the host's immune response in demyelination. In addition, other studies have indicated that HSV travels from the site of peripheral infection to the PNS and then to the CNS where it infects and lyses astrocytes. The infection and subsequent lysis of astrocytes occurs prior to the appearance of demyelination (21, 22). Thus HSV-induced demyelination may also be due, in part, to a cytocidal effect of virus replication in astrocytes and oligodendrocytes in the CNS.
The role of immunopathology in HSV-induced CNS demyelination is one reason why HSV infection serves as a useful model for studies investigating human demyelinating diseases such as Bell's Palsy and multiple sclerosis (23). In addition, studies on the mechanism of CNS demyelination and long-term effects of demyelination may serve as good models for trigeminal neuralgia (24).