Establishment of a hNOK/B51Tg mouse model for the analysis of HIV-1 infections.

<p>NOK/B51Tg mice were established by backcrossing NOK mice with HLA-B*51:01 transgenic NOD/SCID mice, and then were analyzed for the expression of HLA-B51 molecules on their splenocytes. (A) Representative data on the expression of HLA-B51 molecules on splenocytes from a NOK/B51Tg mouse. Splenocytes were stained with TU109 mAB (black line) or isotype control (gray line). hNOK/B51Tg mice were analyzed for the frequency of reconstituted human cells at 10 weeks after the transplantation with human CD34⁺ cells. (B) Representative data and summary of the frequency of human CD19⁺ and CD3⁺ cells among the CD45⁺-gated subset in PBMCs (n = 18). (C) Representative data and summary of the frequency of human CD4⁺ and CD8⁺ T cells among CD45⁺/CD3⁺-gated subsets in PBMCs from hNOK/B51Tg mice (n = 18). hNOK/B51Tg mice were infected with HIV-1 at 14 weeks after the transplantation of CD34⁺ HSCs. (D) HIV-1-infected hNOK/B51Tg mice were analyzed for HIV-1 RNA and plasma viral load at 0, 2, 4, and 6 weeks post-infection (n = 11). (E) Representative data on human CD4⁺ and CD8⁺ T cell populations among CD45⁺/CD3⁺-gated subsets in PBMCs from an HIV-1-infected hNOK/B51Tg mouse (upper data) and from an uninfected one (lower data). (F) Summarized results on human CD4/CD8 T cell ratio at 0, 2, 4, and 6 weeks post-infection for PBMC from HIV-1-infected hNOK/B51Tg mice (n = 11, black circles) and from uninfected ones (n = 8, white circles). In uninfected hNOK/B51Tg mice, the proportion of human T cells in PBMC from the mice was observed from 14 weeks to 20 weeks after the transplantation. Asterisks indicate statistically significant differences (*<i>p<0.05</i>, HIV-1-infected hNOK/B51Tg mice <i>vs.</i> uninfected ones). Error bars represent SEMs. (G) The number of human CD4⁺ T cells in peripheral blood from HIV-1-infecetd hNOK/B51Tg (n = 8, right data) and uninfected ones (n = 6, left data) was determined. Asterisks indicate statistically significant differences (*<i>p<0.05</i>, HIV-1-infected hNOK/B51Tg mice at 2, 4, or 6 post-infection <i>vs.</i> hNOK/B51Tg mice before an HIV-1 infection).