Research ArticleVIROLOGY

The clonal repopulation of HSPC gene modified with anti–HIV-1 RNAi is not affected by preexisting HIV-1 infection

See allHide authors and affiliations

Science Advances  22 Jul 2020:
Vol. 6, no. 30, eaay9206
DOI: 10.1126/sciadv.aay9206


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.

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

View Full Text

Stay Connected to Science Advances