MOESM2 of HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds

Additional file 2: Figure S2. Neutralization sensitivity of viral isolates for bNAbs. Clonal HIV-1 variants from 7 and 11 months post-SC were tested for their neutralization sensitivity for mAbs PGT121, PGT126, PGT128, 2G12, VRC01, PG9 and 8ANC195. The IC50 values are plotted and the horizontal bars represent the median IC50 value

MOESM4 of HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds

Additional file 4: Figure S4. bNAb epitopes and the corresponding viral sequence alignment. Amino acid sequences of bNAb epitopes for isolates from 7 and 11 months post-SC. Contact residues (<5.0 Å distance from gp120 residues based on the crystal structures of gp120-bNAb co-complexes [60, 121, 122, 124] are indicated with black dots for (A) PGT135, (B) b12 (grey), 12A21 and (C) PG16

MOESM5 of HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds

Additional file 5: Figure S5. Schematic representation of the V1V2 loop observed in D16916. Schematic of the V1V2 loops based on Bontjer et al. [125]. Cysteine residues and disulfide bridges are indicated in red. The variable loops are depicted in yellow and the conserved bridging sheet β-strands 2 and 3, are indicated in green. (A) V1V2 loop containing the normal number of cysteine residues. (B) V1V2 loop with 2 additional cysteine and adjacent residues, forming an “oven mitt” structure. (C) V1V2 loop with 2 additional cysteine and adjacent residues, resulting in a longer V1 compared to (A). (D-E) V1V2 with 4 additional cysteine and adjacent residues forming two “oven mitt” structures, (F) or an alternative structure

Characteristics of the study population.

<p>Groups of participants with genital viral load (GVL) < 40 HIV RNA copies/mL (N = 132) versus GVL≥40 HIV RNA copies/mL (N = 111) at baseline are compared. Comparison is made using t-test for continuous and Chi-square for dichotomous variables. Significant differences are highlighted with*.</p><p>Characteristics of the study population.</p

Cohort profile.

<p>This flow chart provides information on the number of patients recruited, eligible for antiretroviral therapy and who had viral load and CD4 data available at baseline and at month 12. Patients were classified in groups of genital viral load (GVL) <40 RNA copies/ml and GVL ≥40 copies /mL.</p

Changes in proportion of detectable cytokine levels from baseline to month 12 in participants receiving ART,

<p>Only cytokines analyzed as dichotomous variable are included in this table. Changes of proportion of women with detectable cytokines are compared between baseline and month 12 using McNemar. No significant differences were found. Results on cytokines analyzed as continuous variables are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127201#pone.0127201.g002" target="_blank">Fig 2</a>.</p><p>Changes in proportion of detectable cytokine levels from baseline to month 12 in participants receiving ART,</p

Changes of biological marker levels in the genital compartments between baseline and month 12 among study participants receiving anti-retroviral therapy.

<p>Changes of genital (GVL) and plasma viral loads (PVL), CD4 counts and cytokines levels analysed as continuous variables were compared between baseline and month 12 in patients receiving antiretroviral therapy. Thin broken lines represent the change in immune parameter of a study participant between the two measurement times and the thick solid line in red is the average change in the parameter between the two time points. P values were calculated using the paired t-test and are displayed inside each graph. GVL, PVL and CD4 counts changes were significant, whereas cytokines levels remained comparable at baseline and month 12.</p

Predictors of GVL at baseline and at month 12 among participants receiving ART.

<p>Predictors of genital viral load ≥40 copies/mL at baseline and at month 12 were determined. Ninety six women initiating ART were included in the analysis at baseline. Forty-nine women receiving ART had viral load data available at month 12 and were included in the analysis at month 12. The variables included were:</p><p>At baseline: Plasma viral load, CD4, age, IL-8, IP-10, MIP-1b, VEGF, IL-6, GCSF, IL-1β, <i>N</i>. <i>gonorrhoea</i>, <i>Chlamydia trachomatis</i>, <i>Trichomonas vaginalis</i>, HSV2</p><p>At month 12: Use of family planning method, marital status, <i>Trichomonas vaginalis</i> at baseline & month 12, IL-8 at baseline & month 12, IP-10 at baseline & month 12, MIP-1b at month 12, IL-1β at month 12, IL-1RA at month 12, IL-6 at month 12, Genital VL at baseline, plasma VL at month 12.</p><p>AIC: Aikaike Information criteria.</p><p>Predictors of GVL at baseline and at month 12 among participants receiving ART.</p

Relationship between plasma IP-10 levels and cell-associated DNA levels during primary HIV-1 infection.

<p><b>A.</b> IP-10 plasma concentrations stratified on cell-associated DNA levels during PHI (M0). <b>B.</b> Correlation between IP-10 concentrations and cell-associated DNA levels during PHI (M0). M0 = primary HIV-1 infection and time of inclusion (Fiebig stage III/IV).</p

Blood IP-10 levels in patients with controlled HIV viremia.

<p><b>A.</b> IP-10 levels were determined in plasma in a longitudinal study, before treatment initiation and after >24 months of antiretroviral treatment, in comparison to HIV-negative individuals. The median (IQR) IP-10 values were 35.3 (10.9–51.6), 190.2 (78.3–269.7) and 97 (63.4–141.7) in HIV-, cART-naïve (VIR) and cART-treated individuals, respectively. IP-10 levels fell in cART-treated patients. B. Comparison of IP-10 levels during primary (PHI), post-acute (M6) and chronic HIV-1 infection (HIC, VIR) by comparison with cART-treated patients. HIC<50 and HIC>50 respectively represent HIV controllers with HIV RNA < and > 50 copy numbers/ml. <b>C.</b> Correlation between plasma IP-10 levels and CD4 cell counts during treatment. <b>D.</b> Correlation between plasma IP-10 levels and CD4 counts during treatment, considering only individuals with CD4>500 (25 patients). BL = baseline levels before antiretroviral treatment, cART = combination antiretroviral treatment, HIV- = HIV negative, PHI M0 = Primary HIV-1 infection time of enrollment in the PRIMO cohort, M6 = 6 months post M0/PHI, VIR = viremic cART-naïve patients, HIC = HIV controllers, ***p<0.0001, ****p<0.00001. n = number of individuals.</p