INSECT-TRANSMITTED VERTEBRATE VIRUSES - ALPHATOGAVIRUSES

Alphatogaviruses, of which Sindbis virus (SV) is the prototype, replic ate to high titer in the laboratory both in mosquito cells and in vert ebrate cells. By studying the replication of SV in mosquito cells as w ell as in vertebrate cells, we were able to obtain several viral mutan ts which have novel phenotypes and have contributed to our basic knowl edge of this virus family. These include three host range mutants: SV( AP15/21) which replicates normally in mosquito cells but is restricted in vertebrate cells and SV(CL35) and SV(CL58), which are restricted i n mosquito cells but replicate normally in vertebrate cells. As well, two other mutants are described here: SV(LM21), which can replicate in methionine-starved mosquito cells and SV(MPA), which can replicate in mosquito cells treated with mycophenolic acid or ribavirin. The causa l mutations of both SV(LM21) and SV(MPA) are within the sequence encod ing the nonstructural protein nsP1; these and other findings have enab led us to associate the capping and methylation of the viral mRNAs wit h the nsP1 protein. Our work serves to emphasize that it is both worth while and important to study the replication of arthropod-borne viruse s in cells derived from the arthropod host as well as in cells derived from the vertebrate host.