The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection
2020
Despite advances in hematopoietic stem/progenitor cell (HSPC) transplant for HIV-1–infected patients, the impact of a preexisting HIV-1 infection on the engraftment and clonal repopulation of HSPCs remains poorly understood. We have developed a long terminal repeat indexing-mediated integration site sequencing (LTRi-Seq) method that provides a multiplexed clonal quantitation of both anti–HIV-1 RNAi (RNA interference) gene-modified and control vector-modified cell populations, together with HIV-1–infected cells—all within the same animal. In our HIV-1–preinfected humanized mice, both therapeutic and control HSPCs repopulated efficiently without abnormalities. Although the HIV-1–mediated selection of anti–HIV-1 RNAi-modified clones was evident in HIV-1–infected mice, the organ-to-organ and intra-organ clonal distributions in infected mice were indistinguishable from those in uninfected mice. HIV-1–infected cells showed clonal patterns distinct from those of HSPCs. Our data demonstrate that, despite the substantial impact of HIV-1 infection on CD4+ T cells, HSPC repopulation remains polyclonal, thus supporting the use of HSPC transplant for anti-HIV treatment.
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