Fig 1.
Early features of HIV infection in the blood of NSG HuMice.
Frequencies of CD3+ T cells (a) and CD19+ B cells (b) in CD45+ humans cells from the blood of NSG HuMice infected at 19 weeks of age (D0 on the graph) (c) Frequencies of CD4+ T cells in CD45+CD3+ human cells in the blood relative to the day of infection. The p value is from a linear regression analysis. (d) Viral loads (VL) in the blood of HIV-infected NSG HuMice was determined by the Cobas PCR at the time indicated in the legend. Results shown in c and d are from 2 independent experiments. (e) Correlation between viral loads (VL) and frequency of CD4+ T cells at 30 days post-infection with 10 to 50 ng p24 of CCR5-tropic HIV. Results shown are cumulative from 4 independent experiments with HuMice aged from 19 to 28 weeks of age when infected. Each dot represents a single mouse. (f) Correlation between viral loads (VL) and absolute numbers of CD4+ T cells in the blood of HuMice infected with 50 ng p24 of CCR5-tropic HIV at 25 weeks of age. Results represent cumulative values obtained at 14 and 37 days post infection from a total of 5 mice analyzed in a single experiment. The non-parametric Spearman correlation coefficient and the p value are indicated in panels e and f.
Fig 2.
Impact of CD8 T cell depletion on early viral replication in HIV-infected NSG HuMice
(a) Representative FACS profile of a CD8/CD4 staining in CD45+CD3+ cells from the blood 50 days after injection of PBS or 10 mg/kg of a chimeric anti-CD8 depleting antibody (+MT807R1) in 17 weeks-old NSG HuMice. (b) Viral loads (VL) were determined by Cobas Roche PCR in 17 to 36-weeks old NSG HuMice infected with 15 to 25 ng p24 of CCR5-tropic viruses 3 days after injection of PBS or the CD8-depleting antibody (CD8-depleted) (c) Area under the curve (AUC) was determined based on viremia in the blood of HuMice treated with PBS or the CD8-depleting antibody (CD8-depleted) and infected 3 days later with a CCR5-tropic HIV (Bal or NL4A8). (n.s = p>0.05 from a Mann-Whitney test).
Fig 3.
Specific deletion of CD4+CCR5+ T cells in the periphery but not in the blood.
Frequencies of CCR5+ in CD45+CD3+CD4+ T cells (a) and of CD4+ in CD45+CD3+ T cells (b) measured in the blood before and 23 days after infection of HIV-infected NSG HuMice (ns = not significant from a Wilcoxon matched-pairs signed rank test) (c) A representative FACS profile showing depletion of CCR5+ cells in the spleen of an infected animal is pictured. Numbers indicate the frequency of positive-cells in the depicted gate. FMO = Fluorescence minus one (d) Frequencies of CCR5+ cells in human CD45+CD3+ cells from the spleen and the bone marrow (BM) 37 days after HIV infection (HIV+). In this experiment, 25 weeks-old NSG HuMice were infected with 50 ng p24 of CCCR5-tropic HIV. Control mice (HIV-) are non-infected NSG HuMice from two independent experiments euthanized at 13 and 17 weeks of age. Statistical significance was determined using the Holm-Sidak method, with alpha = 5.0%.