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Of C57BL\/6 mice infected with low doses (10<jats:sup>2<\/jats:sup>\u221210<jats:sup>6<\/jats:sup> PFU) of either virus, 30\u221240% develop encephalitis and die within 10\u221212 days<jats:sup>1<\/jats:sup>, <jats:sup>2<\/jats:sup>. Mice with defects in the Fas or granule exocytosis (perforin and granzymes A and B) pathway of cellular cytotoxicity display reduced mortality and increased survival time when infected with MVE and are protected from encephalitis when deficient in both pathways. This contrasts with infection with WNV where defects in these cytolytic mechanisms increase the percentage of mice that succumb to encephalitis. Thus, no generalizations as to protective or detrimental effects of cytolytic effector functions in recovery from closely related flavivirus infections can be made. 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