EXTREME FITNESS DIFFERENCES IN MAMMALIAN AND INSECT HOSTS AFTER CONTINUOUS REPLICATION OF VESICULAR STOMATITIS-VIRUS IN SANDFLY CELLS

Continuous, persistent replication of a wild-type strain of vesicular stomatitis virus in cultured sandfly cells for 10 months profoundly de creased virus replicative fitness in mammalian cells and greatly incre ased fitness in sandfly cells. After persistent infection of sandfly c ells, fitness was over 2,000,000-fold greater than that in mammalian c ells, indicating extreme selective differences in the environmental co nditions provided by insect and mammalian cells. The sandfly-adapted v irus also showed extremely low fitness in mouse brain cells (comparabl e to that in mammalian cell cultures). It also showed an attenuated ph enotype, requiring a nearly millionfold higher intracranial dose than that of its parent clone to kill mice. A single passage of this adapte d virus in BHK-21 cells at 37 degrees C restored fitness to near neutr ality and also restored mouse neurovirulence. These results clearly il lustrate the enormous capacity of RNA viruses to adapt to changing sel ective environments.