Dataset Information

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

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-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.

SUBMITTER: Zou W

PROVIDER: S-EPMC8686389 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Zou Wei W Xing Juanjuan J Zou Shijie S Jiang Mei M Chen Xinping X Chen Qi Q Liu Daozheng D Zhang Xiangcheng X Fu Xin X

Biology direct 20211220 1

<h4>Background</h4>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.<h4>Results</h4>In the current study we investigated the influence of HIV-1<sub>LAI</sub> Nef (L ...[more]

PMID: 34930406

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Project description:Programmed cell death-2 (PDCD2) protein is enriched in embryonic, hematopoietic, and neural stem cells, however, its function in stem/progenitor cell differentiation is unclear. We investigated the effects of PDCD2 knockdown on the development and differentiation of hematopoietic progenitor cells (HPC). CD34(+) cells derived from normal human bone marrow and K562 leukemic cells were effectively transduced with short-hairpin RNA to knockdown PDCD2. Colony-forming assays were used to investigate the effects of PDCD2 loss on HPC clonogenic potential and on 12-O-tetradecanoyl-phorbol-13-acetate-and arabinofuranosylcytosine-induced terminal differentiation. In CD34(+) clonogenic progenitors, PDCD2 knockdown decreased the total number of colony-forming units, increased the number of colony-forming units-granulocyte-erythroid-macrophage-megakaryocyte and burst-forming unit-erythroid primitive colonies, and decreased the number of burst-forming unit-erythroid mature colonies. Similar results were observed in K562 cells, suggesting that PDCD2 is important for HPC differentiation and/or survival, and for erythroid lineage commitment. Furthermore, 12-O-tetradecanoyl-phorbol-13-acetate-induced megakaryocytic differentiation and proliferation of K562 cells was not affected by PDCD2 knockdown. In contrast, arabinofuranosylcytosine-induced erythroid differentiation of K562 cells was significantly reduced with PDCD2 knockdown, with no effect on cell proliferation. The effects of PDCD2 knockdown were attributed to a cell cycle arrest at G(0)/G(1), along with increased messenger RNA expression of early progenitor factors c-MYB and GATA-2, and decreased expression of erythroid factors GATA-1, EpoR, and ?-globin. We conclude that PDCD2 loss of function(s) impedes erythroid differentiation by inducing cell cycle arrest and increasing expression of early hematopoietic progenitor factors. These findings suggest that PDCD2 has a novel regulatory role in human hematopoiesis and is essential for erythroid development.

Dataset Information

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

Background

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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