Sindbis virus mutants able to replicate in methionine-deprived Aedes albopictus cells

Previous work from this laboratory has shown that the replication of Sindbis virus (SV) in Aedes albopictus cells is sensitive to methionine withdrawal. This sensitivity is thought to reflect a diminished concentration of S-adenosylmethionine (Ado Met) resulting from methionine starvation. Serial passage of SV on Ae. albopictus cells maintained in low concentrations of methionine gave rise to a population of mutants whose replication in mosquito cells was resistant to methionine starvation. In vertebrate cells, these mutants were also resistant to inhibition by cycloleucine. We favor the hypothesis that the adaptation to low methionine reflects the accumulation of mutations resulting in a viral RNA "cap" methyltransferase with an increased affinity for Ado Met.