SPREAD OF MEASLES-VIRUS THROUGH AXONAL PATHWAYS INTO LIMBIC STRUCTURES IN THE BRAIN OF TAP1- -MICE/

The spread of measles virus into the brain was studied exploiting the olfactory pathway, which represents an important route of neuroinvasio n by viruses. The virus was injected into the main olfactory bulb of w ild-type mice and mice with disrupted TAP1 gene (TAP refers to the Tra nsporter associated with Antigen Presentation), which codes for produc ts essential for the cell-mediated immune response. Virus invasion was monitored for 4 weeks by immunohistochemistry. The distribution of me asles virus was found to be restricted to brain areas connected with t he olfactory bulbs. However, in the wild-type mice there was a marked infiltration of lymphocytes in the infected brain structures, and the virus did not pass beyond the piriform cortex. In the TAP1 -/- mice th e virus spread more extensively along olfactory projections into the l imbic system and monoaminergic brainstem neurons. Infected mice of bot h types developed seizures, which may have been focally evoked from th e piriform cortex. This study provides evidence that measles virus can spread through axonal pathways in the brain. The findings obtained in the gene-manipulated mice point out that a compromised immune state o f the host may potentiate targeting of virus to the limbic system thro ugh olfactory projections. (C) 1997 Wiley-Liss, Inc.