A domainofhumanimmunodeficiency virustype1Vprcontaining repeated H(S/F)RIGaminoacidmotifs causescellgrowtharrest andstructural defects

ABSTRACT Vpris avirion-associated protein ofhumanimmunodeficiencytype 1 (HIV-1)whosefunctioninacquiredimmunodeficiency syndrome (AIDS) has been uncertain.Employing the yeast Saccharomyces cereviswae as a model toexamine the effects of HIV-1 auxiliary proteins on basiccellular functions, we found that the vpr gene caused cellgrowth arrest and structural defects indicated by osmotic sensitivity andgross cell enlargement. Productionofvariousdomainsbygene expression showedthatthiseffect arose fromwithin the carboxyl-terminal third of the Vpr protein andimplicated the sequence HFRIGCRHSRIG, containing two H(S/F)RIG motifs. Electroporation with a series of peptides containingthesemotifscausedstructuraldefectsinyeastthatresulted in osmotic sensitivity. A protein with functionsrelating to theyeastcytoskeleton, Saclp[Cleves, A.E., Novick, P.J. &Bankaitis, V.A. (1989) J. CeUBiol. 109, 2939-2950], showssequence similarity to Vpr, and Vpr's effectinyeastmaybe to disrupt normal Saclpfunctions. The