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

Biol Direct. 2021 Dec 20;16(1):27. doi: 10.1186/s13062-021-00317-3.

Abstract

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-1LAI 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.

Keywords: Differentiation; Hematopoietic stem/progenitor cells; Humanized mouse model; LAI Nef; Myeloid-erythroid lineage cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • HIV-1*
  • Mice
  • Stem Cells
  • nef Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • nef Gene Products, Human Immunodeficiency Virus