In Vitro Selection of an Attenuated Variant of Sindbis Virus: Investigation of the Molecular Basis for Attenuation.

摘要

Adaptation of virulent viruses to an alternate host, either animal or tissue culture, has long been recognized as a means of attenuating virulence for the natural host. The molecular mechanism(s) involved in attenuation by blind passage in tissue culture is not understood. One explanation for this phenomenon is that virus replication involves many specific interactions between virus-derived and host-derived products. Selection in a particular host cell for virus mutants which have an increased efficiency in one or more of these virus-host interactions is though to reduce the efficiency of the analogous interaction in another host cell type. We reasoned that if adaptation to specific host factors were involved in attenuation, then one could apply a selective pressure to enrich the population for virus mutants which exhibited the most efficient interaction with those factors. Efficient virus-cell interaction should lead to more rapid virus growth. Accordingly, we selected for those individuals in the SB population capable of the most rapid growth in BHK cells. We found that a stringent selection pressure for rapid growth led to early and significant attenuation of the virus.