Table 1.
Transmission pair information.
Figure 1.
Plasma viral load and CD4 count in the two recipients during the first year of infection.
Plasma viral load in RNA copies/ml is plotted on a log10 scale along the left vertical axis, while the CD4 T cell count in cells/µl is plotted along the right vertical axis. Time is indicated along the horizontal axis as days post-Fiebig Stage I/II in each recipient. The solid circles represent the longitudinal CD4 counts; the open circles represent plasma viral load. (A) HIV-1 elite controller R880F (B) HIV-1 rapid progressor R463F.
Figure 2.
Kinetics of in vitro replication of viruses recovered from the earliest-available plasma samples from R880F and R463F and IMCs corresponding to each subject's deduced T/F virus sequence.
(A and B). Infection with virus isolates (A) or PBMC stocks derived from IMCs (B) was performed in either pools of human CD8 depleted PBMC isolated from 3 individual donors (A) or single individuals (B), and the data is representative of at least 3 independent experiments for each. Reverse transcriptase activity (measured in digital light units (DLU) or p24 antigen is plotted on a log10 scale on the vertical axis against days following infection of cells in in vitro culture. HIV-1 NL4.3 is shown in (A) as a positive control for in vitro replication. (C). Analysis of the in vitro growth rates of viruses R880 and R463 from each of 9 experiments. The growth rate of each was calculated as the slope of increase in the logarithms of p24 or RT activity over the times when this increase was linear. A Wilcoxon signed-rank test was used to compare the ratios obtained in the experiments. (D). A competition growth assay was performed in triplicate as described in Methods with approximately equal input copies of R880F and R463F viral stocks. Relative amounts of each virus at days 2, 4, 6, 8, and 10 were determined by qPCR. (E). An amino acid sequence alignment of the B*5703 Gag CD8 T cell epitopes for the R880 transmission pair is shown.
Table 2.
Defined T cell targets in individual R880F.
Table 3.
Defined T cell targets in individual R463F.
Figure 3.
T cell response kinetics during acute and early HIV-1 infection.
For both R880F (A) and R463F(B), individual peptide response magnitudes in an IFNγ ELISpot assay are shown as a percentage of the overall response. The insert shows the number of peptide responses detected and the total response magnitude (SFC/106 PBMCs) at each of the time points tested. The sequences of the peptides are shown in Table 2.
Table 4.
Response and escape kinetics in individual R880F.
Table 5.
Response and escape kinetics in individual R463F.
Figure 4.
Longitudinal autologous neutralizing antibody IC50 titer during the first year of infection.
(A). The IC50 neutralizing titer (plasma dilution) against the T/F virus Env-pseudotyped HIV-1 derived from either R463F or R880F is plotted on the vertical axis on a log scale. R463F is depicted by open triangles; R880F is depicted by open squares. These experiments were replicated independently at least 3 times. (B). Heat map showing autologous neutralizing Ab activity versus Envs sampled during the first year of infection. Upper Panel R880F, Lower Panel R463F. Plasma sample dates (post-Fiebig I/II) are shown across the top, and Env clones used as pseudotypes from each time point are shown on the left. Green indicates IC50 Ab titers less than 1∶100; yellow indicates IC50s between 1∶100–1∶1000; orange indicates IC50s between 1∶1000–1∶10,000; red indicates IC50s>1∶10,000.