The configuration of Sindbis virus envelope proteins is stabilized by the nucleocapsid protein.

We have previously provided evidence that a strong and precise interaction of the Sindbis virus nucleocapsid with the cytoplasmic tail of E2 is critical for the function of the mature virion and that changes in this association may affect infectivity (21). In this study, we examined the effects of temperature-sensitive defects in capsid protein on virus infectivity and glycoprotein function. The two Sindbis virus mutants chosen were ts2 and Ser180/Gly183, which contain amino acid substitutions in their capsid proteins. Heating these mutants to 60 degrees C results in a loss of infectivity significantly greater than the loss observed in wild type viruses. Viral glycoprotein-mediated fusion from without using heat-treated virions occurs normally with wild type viruses but is lost in the mutants. These results suggest that defects in the capsid protein can induce a loss of infectivity through secondary conformational changes in the virus envelope glycoproteins and that the function of the virus envelope is dependent upon specific capsid-E2 interactions.