HIV-1(LAI) Nef blocks the development of hematopoietic stem/progenitor cells into myeloid-erythroid lineage cells

BACKGROUND: A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection. RESULTS: In the current study we investigated the influence of HIV-1(LAI) Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs. CONCLUSIONS: Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-021-00317-3.