SIVcpz closely related to the ancestral HIV-1 is less or non-pathogenic to humans in a hu-BLT mouse model

Figures & data

Hu-BLT mice used in this study

Animal ID	% hCD45^+/(hCD45^+ and mCD45^+ cells)	%hCD3^+ in hCD45^+	%hCD8^+ in hCD45^+hCD3^+ cells	%hCD4^+ in hCD45^+ hCD3^+ cells	Experimental group
HM658	50.3	54.5	19.1	77.2	HIV-1
HM660	50.1	80.9	16.4	80.2
HM662	63.9	40.4	21.5	74
HM670	69.3	75.1	17.2	79.4
HM695	57	55.9	13.5	85.2
Avg	58.12	61.36	17.54	79.2
HuM 623	79.9	64.6	17.8	81.6	MB897
HuM 624	84.1	63.9	14.5	84.7
HuM 627	88.1	67	13.3	85.7
HuM 628	62.7	57.8	15.6	83.1
HuM 629	75	67.5	12.1	86.7
Avg	77.96	64.16	14.66	84.36
HuM 632	59.2	62.3	12.7	82.8	EK505
HuM 634	76.3	70.4	11.4	87.6
HuM 635	50.7	51.2	20.9	77.3
HuM 639	60	75	12.7	86.1
HuM 640	79.7	73.6	13.5	85.7
Avg	65.18	66.5	14.24	83.9
HM709	55.1	64.5	12.7	80.9	MT145
HM714	80.4	92.7	16.9	80.2
HM718	50.1	88	15.3	80.3
HM719	55.9	79.6	13	83.3
HM723	50.1	85.9	15.1	82.5
Avg	58.32	82.14	14.6	81.44
HM698	56.4	65	12.1	82.2	BF1167
HM702	50.6	56.5	16.5	75.6
HM703	76.8	77.8	13.6	83.3
HM706	68.7	64.9	13.7	82
HM708	50.8	68.2	15.1	79.8
Avg	60.66	66.48	14.2	80.58
HuM 620	79.5	58.2	20.3	78.5	Negative
HuM 621	82.1	57	20.4	78.9
HuM 622	86.4	69.4	11.7	87.3
Avg	82.67	61.53	17.47	81.57

Fig. 1 Plasma viral load and CD4+ T-cell kinetics in hu-BLT mice infected with HIV-1 or one of four different strains of SIVcpz.

(A) Mean plasma VL kinetics over the course of 16 weeks pi. Five groups of hu-BLT mice (n = 5/each group) were inoculated with a high dose of SIVcpz closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505), two lineages of SIVcpz strains that have not been associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), and HIV-1. Each group is color coded. The dashed line indicates the detection limit of pVL. Statistical significance is indicated with stars. NS non-significance, *<0.05, **<0.01, ***<0.001. (B) CD4+ T-cell depletion in four different SIVcpz- and HIV-1-infected hu-BLT mice. The CD4+ T-cell percentage in the total T cells of five groups of infected hu-BLT mice were quantified. Each group is color coded. Statistical significance is indicated with stars. NS non-significance, *<0.05, **<0.01, ***<0.001

Fig. 2 CD4+ T cells in splenic tissues of SIVcpz- and HIV-1-infected hu-BLT mice at 16 wpi.

CD4+ T cells in whole sections of splenic tissues were detected using immunohistochemical staining. CD4+ T cells are stained blue. Scale bar, 200 µm

Fig. 3 Quantification of CD4+ T cells in splenic tissues of SIVcpz- and HIV-1-infected hu-BLT mice.

(A) The CD4+ T-cell percentage in the total T cells from splenic tissues of each group (n = 5) were quantified using flow cytometry at 16 wpi. (B) CD4+ T-cell counts per square millimeter of spleen tissues were quantified after IHCS at 16 wpi. Statistical significance is indicated with stars. NS non-significance, *<0.05, **<0.01, ***<0.001

Fig. 4 CD4+ T-cell activation in SIVcpz- and HIV-1-infected hu-BLT mice.

CD38+ HLA-DR+ ratios in the CD4+ T cells of the five groups (n = 5/each group) were measured. Each group is color coded. Statistical significance is indicated with stars. NS non-significance, *<0.05, **<0.01, ***<0.001

Fig. 5 Immune activation in splenic tissues of SIVcpz- and HIV-1-infected hu-BLT mice detected using immunofluorescent staining of human CD4 and Ki67.

Human CD4+ T cells are shown in green, human Ki67+ cells in red, and DAPI in blue. Each row is labeled by the virus strain used for infecting the animals. Scale bar, 50 µm

Fig. 6 Quantification of the percentage of Ki67+ cells within CD4+ T cells in splenic tissues of SIVcpz- and HIV-1-infected hu-BLT mice after immunofluorescent co-staining of human CD4 and Ki67.

Statistical significance is indicated with stars. NS non-significance, ***<0.001

Fig. 7 Functional transcriptome comparison of human CD4+ T cells from spleen tissues of SIVcpz- and HIV-1-infected hu-BLT mice.

Heat map of differentially expressed genes (DEGs) in SIVcpz-infected animals compared with HIV-1-infected animals. Log2 fold change is color coded with a range from less than −5 to greater than 5