ANTIGENIC VARIATION OF SIV - MUTATIONS IN V4 ALTER THE NEUTRALIZATIONPROFILE

Antigenic variation is a characteristic feature of lentiviral infectio n. The SIV/macaque model of AIDS provides an ideal system in which to investigate the molecular basis of antigenic variation. The purpose of this study was to genetically map the nucleotide changes in env that alter the neutralization phenotype of SIV. Serum taken from an SIV(mac )239-infected macaque (2D) at 30 weeks postinoculation was found to ne utralize the input virus (SIV(mac)239) and an isolate, P9, obtained at 10 weeks p.i., but did not neutralize two other isolates, P13 and P23 , obtained at 20 and 52 weeks, respectively. Sequence analysis of thes e virus variants revealed clustered amino acid changes in V1 and singl e base pair changes in V2-V4 of P13 and P23. Infectious recombinant vi ruses in which the V1 and V1-V3 sequences of SIV(mac)239 were replaced with those of P13 or P23 retained the neutralization profile of SIV(m ac)239; both were neutralized by macaque 20 serum. Recombinants contai ning the entire surface glycoprotein (gp120) (V1-V5) and the 5' portio n of gp41 of P13 and P23 and those containing gp120 sequences from V4 through the 5' portion of the transmembrane glycoprotein (gp41) were n ot neutralized by 2D serum. Using a panel of monoclonal antibodies in radioimmunoprecipitation assays, P23 and recombinants containing V4 an d V5 of P23 were shown to be antigenically distinct from P13 and SIV(m ac)239. The majority of the amino acid changes in the antigenically di stinct viruses were clustered in V4 (amino acids 413-418) and these ch anges created new potential N-linked glycosylation sites. This study d emonstrates that a small number of specific amino acid changes (amino acids 412 to 418 in the env gene) in the V4 region of the SIV envelope glycoprotein can alter antibody recognition and neutralization and th at these phenotypic changes may be associated with altered glycosylati on of the envelope. (C) 1996 Academic Press, Inc