Divergent effects of chronic HIV-1 infection on human thymocyte maturation in SCID-hu mice

We have recently developed a modified SCID-hu mouse model in which the implanted human thymus and liver (hu-thy/liv) and human peripheral T cells become infected with HIV-1 after i.p. inoculation. By using this model, we evaluated the effect of HIV-1 infection on thymic maturation and observed that different HIV-1 strains had divergent effects of thymic maturation. Although minimal effects on continued thymopoiesis in the hu-thy/liv implant were observed after chronic infection with two primary patient isolates, HIV- 1₂₈ and HIV-1₅₉, and with HIV-1(ADA), HIV-1(Ba-L), HIV-1(JR-CSF), HIV- 1(JR-FL), and HIV-1(SF162), significant thymocyte depletion was detected after infection with HIV-1(IIIB) and HIV-1(RF). Thus, the effect of HIV-1 infection on thymocyte maturation may depend upon the strain of HIV-1 infecting the thymus. Despite the minimal effects on thymopoiesis observed in the hu-thy/liv implanted in SCID-hu mice 6 mo after infection with HIV- 1₂₈, significant changes were seen in the human T cell population circulating in the peripheral blood of these mice. These changes ranged from an inversion of the CD4/CD8 ratio of peripheral human T cells in some SCID- hu mice to the almost complete depletion of peripheral human T cells observed in other SCID-hu mice. Because these effects were associated with the detection of HIV-1 infection of the peripheral human T cells, these modified SCID-hu mice should prove to be a valuable model for investigating the effects of chronic HIV-1 infection on the peripheral human T cell population.