The use of cytochalasins in studies on the molecular biology of virus--host cell interactions

Abstract

In conclusion, one can say that the cytochalasins--in their brief history of application in virology--have proven to be valuable tools in studies on the molecular biology of virus--host cell interactions. On the other hand, viral systems can be useful in defining the primary sites of action of cytochalasins in certain cells. In interpreting the effects of cytochalasins on virus replication, however, one must take into consideration that the cytochalasins exert a wide variety of alterations in cellular functions. Infections by viruses interfere primarily with the synthesis of host DNA, RNA, and proteins. The experiments reviewed here were carried out with different viruses, different cell lines, and--more important--under very different experimental conditions. Nevertheless, a number of informative observations emerge which provide insight into specific aspects of the interaction of viruses with their host cells, and help us to understand the mode of action of cytochalasins on specific cellular functions: Cytochalasins may decrease or increase the competence of cells for infection by viruses. For the DNA viruses, vaccinia virus and adenovirus, cytochalasin treatment of host cells resulted in a reduced virus yield; whereas for the RNA viruses, poliovirus, parainfluenza virus, and VSV, cytochalasin treatment results in an increased virus yield. The precise mechanism by which cytochalasins exert these effects remain unclear. It is proposed that the cytochalasin-mediated enhancement of cell infectibility for poliovirus--the only system for which this effect has been studied in more detail--is primarily due to a reduction of polypeptide chain initiation. This reduction dramatically amplifies the inherent translational advantage of virus mRNAs over host cell mRNAs, resulting in a relative stimulation of viral mRNA translation. The cytochalasin-mediated sensitization of cells for infection by isolated poliovirus RNA is explainable by a comparable effect on protein synthesis. In this case, cytochalasin may act in part by substituting for the function of a viral protein(s). When cytochalasin B is added to cells which have previously been infected by intact HSV, formation of infectious virus particles is severely inhibited...