ArticleJCI insight2022
Type I interferons and TGF-β cooperate to induce liver fibrosis during HIV-1 infection under antiretroviral therapy.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- METTL14 Downregulation Accelerates HBV-Related Cirrhosis and Hepatocellular Carcinoma by Promoting Type I Interferon Release via the cGAS-STING Pathway Through mJournal of medical virology · 2026Article
- Targeting the pDC/IFN-I axis in HIV-1 immunotherapy.Current opinion in HIV and AIDS · 2026Review
- Liver biopsies obtained throughout SIV infection reveal evolving interferon stimulated protein expression within distinct monocyte/macrophage subsets.PLoS pathogens · 2025Article
- CD24-Fc resolves inflammation and enhances anti-HIV CD8 T cells with polyfunctionality during HIV-1 infection under cART.PLoS pathogens · 2025Article
- Review
- Double, double toil and trouble: transforming growth factor beta (TGF-β) in HIV infection.Frontiers in immunology · 2025Review
- YAP mediates HIV-related liver fibrosis.JHEP reports : innovation in hepatology · 2024Article
- Identification of the shared hub gene signatures and molecular mechanisms between HIV-1 and pulmonary arterial hypertension.Scientific reports · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Type I IFN in Glomerular Disease: Scarring beyond the STING.International journal of molecular sciences · 2024Review
- Persistent hepatitis B virus and HIV coinfections in dually humanized mice engrafted with human liver and immune system.Journal of medical virology · 2023Article
- Evaluation of the interaction between tumor growth factor-β and interferon type I pathways in patients with COVID-19: focusing on ages 1 to 90 years.BMC infectious diseases · 2023Article
- Recent Developments in NSG and NRG Humanized Mouse Models for Their Use in Viral and Immune Research.Viruses · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Liver diseases have become a major comorbidity health concern for people living with HIV-1 (PLWH) treated with combination antiretroviral therapy (cART). To investigate if HIV-1 infection and cART interact to lead to liver diseases, humanized mice reconstituted with progenitor cells from human fetal livers were infected with HIV-1 and treated with cART. We report here that chronic HIV-1 infection with cART induced hepatitis and liver fibrosis in humanized mice, associated with accumulation of M2-like macrophages (M2LMs), elevated TGF-β, and IFN signaling in the liver. Interestingly, IFN-I and TGF-β cooperatively activated human hepatic stellate cells (HepSCs) in vitro. Mechanistically, IFN-I enhanced TGF-β-induced SMAD2/3 activation in HepSCs. Finally, blockade of IFN-I signaling reversed HIV/cART-induced liver diseases in humanized mice. Consistent with the findings in humanized mice with HIV-1 and cART, we detected elevated markers of liver injury, M2LMs, and of IFN signaling in blood specimens from PLWH compared with those of healthy individuals. These findings identify the IFN-I/M2LM/HepSC axis in HIV/cART-induced liver diseases and suggest that inhibiting IFN-I signaling or M2LM may provide a novel therapeutic strategy for treating HIV/cART-associated liver diseases in PLWH treated with antiretroviral therapy.
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