Mmp-9 As A Marker For Vaccinia Virus Related Encephalitis

Smallpox vaccination might be associated with adverse reactions, ranging in severity from benign to lethal. One of the most serious complications is postvaccinal encephalitis. The aim of this study was to identify early markers for vaccinia virus (VACV) induced encephalitis. For this purpose we infected mice intracranially with VACV-Lister or VACV-WR. Histopathological analysis showed that following infection with VACV-WR tissue damage in the brain spatially and temporally correlated with virus replication, infiltration of white blood cells and apoptosis. None of the above markers was observed upon infection with the vaccine strain Lister.MMP-9 is a serum factor known for its correlation to BBB integrity and encephalitis in humans. We found that in sera of VACV-Lister infected animals, MMP-9 levels did not change throughout the infection. However, during VACV-WR infection, in the first 2 days levels of MMP-9 were significantly low than the controls and subsequently rose to levels which were significantly higher than the controls. Elevated MMP-9 was associated with damage to the brain and to BBB integrity.In conclusion, efficient virus replication in the brain causes significant brain damage followed by BBB brake-down and release of MMP-9 to the serum, markers which were not observed when the attenuated strain was examined. Thus, we suggest MMP-9 as a possible non-invasive serum indicator for encephalitis caused by VACV virus.