
<ArticleTitle>Protection of neutralization epitopes in the V3 loop of oligomeric human immunodeficiency virus type 1 glycoprotein 120 by N-linked oligosaccharides in the V1 region.</ArticleTitle>
<AbstractText>The V3 region of the human immunodeficiency virus type 1 envelope protein <prot>gp120</prot> constitutes a potential neutralization target, but the oligosaccharide of one conserved N-glycosylation site in this region protects it from neutralizing antibodies. Here, we determined whether N-linked glycans of other <prot>gp120</prot> domains were also involved in protection of V3 neutralization epitopes. Two molecular clones of HIV-1, one lacking three N-linked glycans of the V1 region (HIV-1(3N/V1)) and another lacking three N-linked glycans of the C2 region (HIV-1(3N/C2)), were created and characterized. <prot>gp120</prot> from both mutated viral clones had higher electrophoretic mobilities than <prot>gp120</prot> from wild-type virus, confirming loss of N-linked glycans. Wild-type virus and both mutant clones replicated equally well in established T cell lines and all three viruses were able to utilize <prot>CXCR4</prot> but not <prot>CCR5</prot> as a coreceptor. The induced mutations increased <prot>gp120</prot> affinity for <prot>CXCR4</prot> but caused no corresponding increase in viral ability to replicate in T cell lines. HIV-1(3N/V1) was neutralized at about 25 times lower concentrations of an antibody to the V3 region than were wild-type virus and HIV-1(3N/C2). Soluble, monomeric gp120 from HIV-1(3N/V1) and wild type virus had identical avidity for the V3 antibody, indicating that the V1 glycans were able to shield V3 only in oligomeric but not monomeric <prot>gp120</prot>. In conclusion, one or more N-linked glycans of <prot>gp120</prot> V1 is engaged in protection of the V3 region from potential neutralizing antibodies, and this effect is dependent on the oligomeric organization of <prot>gp120</prot>/<prot>gp41</prot>.</AbstractText>
