989
Views
6
CrossRef citations to date
0
Altmetric
Original Articles

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

, , , & ORCID Icon
Pages 1-12 | Received 07 Nov 2017, Accepted 25 Feb 2018, Published online: 04 Apr 2018

Figures & data

Hu-BLT mice used in this study

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. 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. 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. 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. 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. 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. 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

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