WEST NILE VIRUS NEUROINVASION AND ENCEPHALITIS INDUCED BY MACROPHAGE DEPLETION IN MICE

The encephalitic West Nile virus and its nonneuroinvasive variant, WN- 25, were used to study the effect of macrophage depletion on viral inv asion of the central nervous system. The in vivo elimination of macrop hages was achieved by use of liposome-encapsulated drug dichloromethyl ene diphosphonate. Depletion of macrophages had an exacerbating effect on the course of the viral infection, exhibited by higher and extende d viremia and accelerated development of encephalitis and death. Using a low dose of West Nile virus (5 PFU/mouse), an increase in mortality (from 50% to 100%)due to macrophage depletion was demonstrated. Furth ermore, the attenuated noninvasive variant WN-25 showed high and prolo nged viremia in the macrophage depleted mice (approximate to 5 log 10 PFU/ml versus 2 in control mice), that allowed the penetration of the virus into the central nervous system. The mortality rate caused by th e attenuated virus in the macrophage-depleted mice was 70-75%, as comp ared to complete survival in the control inoculated mice. These result s indicate a significant role of macrophages in the non-specific immed iate defence system of the organism in case of viral infection.