The clonal repopulation of HSPC gene modified with anti-HIV-1 RNAi is not affected by preexisting HIV-1 infection.
Sci Adv
; 6(30): eaay9206, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32766447
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Transplante de Células-Tronco Hematopoéticas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos