HIV-1 Tat protein inhibits the hematopoietic support function of human bone marrow mesenchymal stem cells.
Virus Res
; 273: 197756, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31521762
ABSTRACT
Most HIV-1-infected patients experience hematopoiesis suppression complications. Bone marrow mesenchymal stem cells (BMSCs) are involved in regulation of hematopoietic homeostasis, so we investigated the role of Tat, a protein released by infected cells in bone marrow and impacted differentiation potential of mesenchymal stem cells, in the BMSC hematopoietic support function. BMSCs were treated with HIV-1 Tat protein (BMSCTat-p), transfected with HIV-1 Tat mRNA (BMSCTat-m) or treated with solvent (PBS) (BMSCcon) for 20 days. Then, the hematopoietic support function of BMSCTat-p, BMSCTat-m and BMSCcon was analyzed via ex vivo expansion of hematopoietic stem cells (HSCs) grown on the BMSCs and via in vivo cotransplantation of HSCs and BMSCs. In addition, the hematopoiesis-supporting gene expression patterns of BMSCTat-p, BMSCTat-m and BMSCcon were compared. The results showed that BMSCTat-p and BMSCTat-m displayed reduced expansion, a decline in the number of colony forming units (CFUs) and a decreased proportion of the primitive subpopulation of hematopoietic stem cells under coculture conditions compared with BMSCcon. The ability of BMSCTat-p to support hematopoietic recovery was also impaired, which was further confirmed by the patterns in gene expression analysis. In conclusion, Tat treatment reduced the function of BMSCs in hematopoietic support, likely by downregulating the expression of a series of hematopoietic cytokines.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Diferenciación Celular
/
Productos del Gen tat del Virus de la Inmunodeficiencia Humana
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Virus Res
Asunto de la revista:
VIROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China