Neutralization of SIVmac239/17E in lymphocyte cultures involves virus strain-specific linear and conformational epitopes encoded by different regions of the env gene including the "V3" domain

Abstract

SIVmac251 and its closely related derivatives SIVmac239 and SIVmac239/17E vary greatly in their susceptibility to neutralization with homologous and heterologous antisera. Whereas SIVmac251 induces homologous neutralizing antibodies, the antibodies induced by SIVmac239 rarely neutralize infectivity of this virus in lymphocyte cultures. In contrast, SIVmac239/17E 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 neutralization of SIVmac239/17E. Using chimeric viruses in which different regions of the env gene of both SIVmac239 and SIVmac239/17E were inserted into a background of either of the parental genomes, we showed that the newly acquired neutralization properties of SIVmac239/17E were attributable to amino acid substitutions between the V2 and V4 regions of gp 120. Site-directed mutagenesis of the env gene in this region 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 neutralization 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 SIVmac251 and both are distinct from SIVmac239.