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. 1998 Oct;72(10):8437-45.
doi: 10.1128/JVI.72.10.8437-8445.1998.

Characterization of simian-human immunodeficiency virus envelope glycoprotein epitopes recognized by neutralizing antibodies from infected monkeys

B Etemad-Moghadam  1 , G B Karlsson, M Halloran, Y Sun, D Schenten, M Fernandes, N L Letvin, J Sodroski
Affiliations

Characterization of simian-human immunodeficiency virus envelope glycoprotein epitopes recognized by neutralizing antibodies from infected monkeys

B Etemad-Moghadam et al. J Virol. 1998 Oct.

Abstract

We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein epitopes recognized by neutralizing antibodies from monkeys recently infected by molecularly cloned simian-human immunodeficiency virus (SHIV) variants. The early neutralizing antibody response in each infected animal was directed mainly against a single epitope. This primary neutralizing epitope, however, differed among individual monkeys infected by identical viruses. Two such neutralization epitopes were determined by sequences in the V2 and V3 loops of the gp120 envelope glycoprotein, while a third neutralization epitope, apparently discontinuous, was determined by both V2 and V3 sequences. These results indicate that the early neutralizing antibody response in SHIV-infected monkeys is monospecific and directed against epitopes composed of the gp120 V2 and V3 variable loops.

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Figures

FIG. 1
FIG. 1
Structure of the SHIV-KB9 and -KB9ct chimeras. The top part of the figure shows the genetic composition of the chimeric SHIV used in this study. The SIVmac239-derived elements of the genome are represented by the shaded rectangles, and the HIV-1-specific components are represented by white rectangles. The circles and triangle mark the coding changes that occurred during animal passage. The white circles represent the nucleotide changes in the LTR; the change in the R region is present in both the 3′ and 5′ LTR, and the substitution in U3 is present only in the 3′ LTR. The triangle marks the 140-bp deletion affecting the HIV-1 gp41 tail. The encoded amino acid substitutions in Tat and the gp41 cytoplasmic tail are present in both KB9 and KB9ct, whereas the env ectodomain changes are present only in KB9. The lower portion of the figure indicates the differences in amino acid composition between KB9 and KB9ct. The sequence of KB9ct in this portion of the envelope glycoproteins is identical to that of 89.6.
FIG. 2
FIG. 2
Temporal emergence of neutralizing antibodies against viruses with homologous envelope glycoproteins. The presence of antibodies able to neutralize recombinant CAT viruses with homologous envelope glycoproteins was assessed by using plasma from infected monkeys at various time points after infection. The horizontal axes designate days postinfection, and the vertical axes show the level of neutralization normalized to the value observed in the presence of preimmune plasma. CEMx174 cells were infected with the respective homologous recombinant viruses in the presence of a 1:50 dilution of plasma from SHIV-KB9ct-infected monkeys (A) or SHIV-KB9-infected monkeys (B). Symbols represent the monkeys designated as shown.
FIG. 3
FIG. 3
Cross-neutralizing activity in plasma from day 71 postinfection. Preimmune plasma and plasma from day 71 postinfection were used in a 1:50 dilution to assess neutralization of viruses with KB9 and KB9ct envelope glycoproteins. Entry of the recombinant CAT viruses with KB9 envelope glycoproteins (top panel) and with KB9ct envelope glycoproteins (bottom panel) is shown. The animal number and the specific SHIV with which it was infected are indicated at the bottom of the figure. P, samples incubated with preimmune plasma; 71, samples incubated with plasma from day 71.
FIG. 4
FIG. 4
Comparative neutralization of recombinant envelope glycoproteins. A panel of recombinant envelope glycoproteins containing amino acids shared with either KB9 or KB9ct was tested for neutralization with plasma samples from the infected monkeys. Plasma samples from day 71 were used in this analysis, and CAT activity was normalized to the value observed in the presence of preimmune plasma for each virus; thus, a value of 1 designates no neutralization. The results of the neutralization assays are shown here for the following animals: KB9ct-infected animals 15865 (A), 11796 (B), 13939 (C), and 13898 (D) and KB9-infected animals 13930 (E), 13921 (F), and 13876 (G). The horizontal axes indicate the various recombinant envelope glycoproteins, and the vertical axes show the level of neutralization normalized to the value observed in the presence of preimmune plasma.
FIG. 5
FIG. 5
Cross-neutralization of viruses with heterologous envelope glycoproteins by plasma from late time points after infection. Plasma samples from time points subsequent to day 71 were tested for neutralization of viruses with both KB9 (□) and KB9ct (⊕) envelopes. The horizontal axes indicate days postinfection. CAT activity was normalized to the value observed in the presence of preimmune plasma and is shown for the following infected animals: KB9ct-infected monkeys 15865 (A), 11796 (B), 13898 (C), and 13939 (D) and KB9-infected animals 13930 (E), 13921 (F), and 13876 (G).
FIG. 6
FIG. 6
Neutralization of viruses with the divergent envelope glycoproteins. Entry of recombinant CAT virus with divergent envelope glycoproteins was tested in the presence of plasma from all infected monkeys at day 71, as well as the latest available time points. Results of neutralization assays using viruses with HXBc2 envelope glycoproteins (A and B), with ELI envelope glycoproteins (C and D), and with MN envelope glycoproteins (E and F) are shown. Horizontal axes designate days postinfection, and vertical axes show the level of neutralization normalized to the value observed in the presence of preimmune plasma. Symbols represent the monkeys designated, as shown.
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