ArticleThe Journal of clinical investigation2008
Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef/PPARgamma/STAT5 signaling pathway in macaques.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 62 citations in OpenAlex.
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- Chronic Myeloid Leukemia, from Pathophysiology to Treatment-Free Remission: A Narrative Literature Review.Journal of blood medicine · 2023Review
- Phenotypical changes of hematopoietic stem and progenitor cells in COVID-19 patients: Correlation with disease status.Central-European journal of immunology · 2023Article
- Consequences of HIV infection in the bone marrow niche.Frontiers in immunology · 2023Review
- Hematopoietic responses to SARS-CoV-2 infection.Cellular and molecular life sciences : CMLS · 2022Review
- Expansion of Immature Neutrophils During SIV Infection Is Associated With Their Capacity to Modulate T-Cell Function.Frontiers in immunology · 2022Article
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- Case 31-2021: A 21-Year-Old Man with Sore Throat, Epistaxis, and Oropharyngeal Petechiae.The New England journal of medicine · 2021Article
- HIV-1 Nef Induces Hck/Lyn-Dependent Expansion of Myeloid-Derived Suppressor Cells Associated with Elevated Interleukin-17/G-CSF Levels.Journal of virology · 2021Article
- PPARγ agonists promote the resolution of myelofibrosis in preclinical models.The Journal of clinical investigation · 2021Article
- Nuclear receptors in podocyte biology and glomerular disease.Nature reviews. Nephrology · 2021Review
- The Dynamic Interface of Viruses with STATs.Journal of virology · 2020Review
- Article
- Comorbidities of HIV infection: role of Nef-induced impairment of cholesterol metabolism and lipid raft functionality.AIDS (London, England) · 2020Review
- Pharmacological Inhibition of PPARy Boosts HIV Reactivation and Th17 Effector Functions, While Preventing Progeny Virion Release and dePathogens & immunity · 2020Article
- A Novel Inhibitor of STAT5 Signaling Overcomes Chemotherapy Resistance in Myeloid Leukemia Cells.Cancers · 2019Article
- Characterization, biology, and expansion of regulatory T cells in the Cynomolgus macaque for preclinical studies.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infection of primates by HIV-1 and SIV induces multiple hematological abnormalities of central hematopoietic origin. Although these defects greatly contribute to the pathophysiology of HIV-1 infection, the molecular basis for altered BM function remains unknown. Here we show that when cynomolgus macaques were infected with SIV, the multipotent potential of their hematopoietic progenitor cells was lost, and this correlated with downregulation of STAT5A and STAT5B expression. However, forced expression of STAT5B entirely rescued the multipotent potential of the hematopoietic progenitor cells. In addition, an accessory viral protein required for efficient SIV and HIV replication and pathogenicity, "Negative factor" (Nef), was essential for SIV-mediated impairment of the multipotent potential of hematopoietic progenitors ex vivo and in vivo. This newly uncovered property of Nef was both conserved between HIV-1 and SIV strains and entirely dependent upon the presence of PPARgamma in targeted cells. Further, PPARgamma agonists mimicked Nef activity by inhibiting STAT5A and STAT5B expression and hampering the functionality of hematopoietic progenitors both ex vivo and in vivo. These findings have extended the role of Nef in the pathogenicity of HIV-1 and SIV and reveal a pivotal role for the PPARgamma/STAT5 pathway in the regulation of early hematopoiesis. This study may provide a basis for investigating the potential therapeutic benefits of PPARgamma antagonists in both patients with AIDS and individuals with hematopoietic disorders.
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