Herpes simplex virus type 1 (HSV 1) induced multifocal demyelination of the central nervous system (CNS) in mice

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Workshop: Molecular Minicry and Virus-lnduced Demyelination HERPES SIMPLEX VIRUS TYPE 1 (HSV 1) INDUCED MULTIFOCAL DEMYELINATIONOF THE CENTRAL NERVOUS SYSTEM (CNS) IN MICE. L.F. Kastrukoff, A. Lau, S.U. Kim. Department of Medicine, Faculty of Medicine, U n i v e r s i t y of B r i t i s h Columbia, Vancouver, Canada. Demyelination at the trigeminal root entry zone (TREZ) in the CNS is observed f o l l o w i n g o r o - f a c i a l

i n o c u l a t i o n of HSV I .

To determine i f path-

ological appearance f o l l o w i n g l i p i n o c u l a t i o n with virus is g e n e t i c a l l y determined, 22 inbred and congenic s t r a i n s of mice were categorized i n t o r e s i s t a n t , moderately r e s i s t a n t , and susceptible groups on the basis of natural resistance to m o r t a l i t y .

The CNS appearance of representative s t r a i n s

of each group, varied from focal c o l l e c t i o n s of mononuclear c e l l s in C57BL/6 mice ( r e s i s t a n t ) and unifocal demyelinating lesions at the TREZ in Balb/c (moderately r e s i s t a n t ) , to m u l t i f o c a l demyelinating lesions throughout the brain in A/J mice ( s u s c e p t i b l e ) . Serial v i r a l t i t r a t i o n

studies in these three s t r a i n s implicate roles

f o r both v i r u s and the immune system in the development of lesions at TREZ. M u l t i f o c a l lesions in the brain appear to be the r e s u l t of immune mechanisms alone but are l i k e l y triggered by the acute i n f e c t i o n . Oligodendrocytes (MOL) derived from d i f f e r e n t s t r a i n s of mice also d i f f e r in resistance to HSV I .

Primary MOL cultures derived from 20 s t r a i n s of mice

were infected and examined s e r i a l l y using immunofluoresence, EM, and TClD50 techniques.

A close c o r r e l a t i o n was observed between results i n - v i t r o and

m o r t a l i t y / p a t h o l o g y i m p l i c a t i n g resistance at t h i s level as playing a role in determining outcome.

Although the c e l l u l a r mechanisms involved in mediating

differences in resistance are unclear, q u a n t i t a t i v e differences in v i r u s production are observed among primary MOL cultures derived from the 3 d i f f e r e n t s t r a i n s of mice.

Furthermore, differences in the transport of v i r u s , observed

by EM, through the cytoplasm to the nucleus of the infected c e l l may also c o n t r i b u t e to the observed differences in resistance.