NEUTRALIZATION OF SIV(MAC)239 17E IN LYMPHOCYTE-CULTURES INVOLVES VIRUS STRAIN-SPECIFIC LINEAR AND CONFORMATIONAL EPITOPES ENCODED BY DIFFERENT REGIONS OF THE ENV GENE INCLUDING THE V3 DOMAIN/

SIV(mac)251 and its closely related derivatives SIV(mac)239 and SIV(ma c)239/17E vary greatly in their susceptibility to neutralization with homologous and heterologous antisera. Whereas SIV(mac)251 induces homo logous neutralizing antibodies, the antibodies induced by SIV(mac)239 rarely neutralize infectivity of this virus in lymphocyte cultures. In contrast, SIV(mac)239/17E is remarkably susceptible to neutralization with homologous and heterologous antisera induced by other strains of SIVmac. In this study, we studied the molecular basis for the neutral ization of SIV(mac)239/17E. Using chimeric viruses in which different regions of the env gene of both SIV(mac)239 and SIV(mac)239/17E were i nserted into a background of either of the parental genomes, we showed that the newly acquired neutralization properties of SIV(mac)239/17E were attributable to amino acid substitutions between the V2 and V4 re gions of gp120. Site-directed mutagenesis of the env gene in this regi on showed that the arginine substitutions at positions 334 and/or 340 within the ''V3'' domain were fundamental to virus neutralization but other substitutions in the V2-V4 region added to the ease of its neutr alization since it became neutralizable with much higher dilutions of serum. The molecular determinants for neutralization of this virus are distinct from those reported as responsible for neutralization of SIV (mac)251 and both are distinct from SIV(mac)239. (C) lees Academic Pre ss, Inc.