Antibodies raised to short synthetic peptides with sequences derived from HIV-1 SF2 gp120 can both neutralize and enhance HIV-1 SF13: a later variant isolated from the same host.
HIV-1 SF13 emerged in a patient with immunity to HIV-1 SF2. This study determined the effect of antibodies raised to HIV-1 SF2 on the replication of the later variant. Antisera in rats were raised previously to a complete set of overlapping, synthetic 15mer peptides following the sequence of HIV-1 SF2 gp120. These sera have now been used in neutralization and enhancement assays against viruses derived from molecular clones of both variants. The sets of peptides inducing neutralizing antibodies to the two variants overlap. Antibodies to the third variable region of HIV-1 SF2 only neutralize the homologous virus whereas those to the second and fourth variable regions neutralize both variants. In contrast, the sets of major epitopes involved in enhancement do not overlap. Epitopes for both variants form two clusters when superimposed on the conformation of the conserved regions. To determine if antibodies with the potential to enhance or neutralize HIV-1 SF2 change over time in infected individuals sera from chimpanzees were used because no material was still available from the original patient. Antibodies to HIV-1 SF2 neutralizing epitopes and HIV-1 SF13 enhancing epitopes were present in the circulation of chimpanzees infected with HIV-1 SF2. Once antibodies to the neutralizing epitopes were induced they persisted whereas antibodies to the enhancing epitopes varied with time after infection. Conditions may therefore exist within individual hosts where not only neutralizing but also enhancing antibodies have the potential to contribute to the selection pressure operating on the circulating population of polymorphic variants.
Davis
D
D
Molecular Immunopathology Unit, MRC Centre, Cambridge, United Kingdom.
Trischmann
H
H
Stephens
D M
DM
Lachmann
P J
PJ
D000818:Animals; D019067:Antibody-Dependent Enhancement / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D014644:Genetic Variation / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D009500:Neutralization Tests; D002679:Pan troglodytes; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012703:Serotyping; D014779:Virus Replication
D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments