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Página principal > Artículos > Artículos publicados > HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients |
Fecha: | 2021 |
Resumen: | Objective: To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients. Methods: We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1. 5 (in either direction) and false discovery rate (FDR) ≤ 0. 05 were identified as significantly differentially expressed (SDE). Results: HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR < 0. 05), one linked to Epstein-Barr virus infection and another related to p53 signaling. For HIV/HCV-f vs. HIV-mono group, we found 44 SDE genes that revealed 31 enriched pathways (FDR < 0. 05) related to inflammation, cancer/cell cycle alteration, viral and bacterial infection, and comorbidities associated with HIV/HCV-coinfection. Five genes were overrepresented in most pathways (JUN, NFKBIA, PIK3R2, CDC42, and STAT3). Conclusion: HIV/HCV-coinfected patients who eradicated hepatitis C with IFN-based therapy showed profound gene expression changes after achieving sustained virological response. The altered pathways were related to inflammation and liver-related complications, such as non-alcoholic fatty liver disease and hepatocellular carcinoma, underscoring the need for active surveillance for these patients. |
Ayudas: | Instituto de Salud Carlos III PI20/00474 Instituto de Salud Carlos III PI17/00657 Instituto de Salud Carlos III PI20/00507 Instituto de Salud Carlos III PI17/00903 Instituto de Salud Carlos III PI18CIII/00020 Instituto de Salud Carlos III PI20CIII/00004 Instituto de Salud Carlos III PI17CIII/00003 Instituto de Salud Carlos III RD16CIII/0002/0002 Instituto de Salud Carlos III RD16/0025/0017 Instituto de Salud Carlos III RD16/0025/0018 Instituto de Salud Carlos III INT16/00100 |
Nota: | Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER). |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | HIV/HCV coinfection ; Gene expression ; Immune system ; HCV clearance ; Interferon therapy ; PBMCs |
Publicado en: | Journal of Biomedical Science, Vol. 28 Núm. 1 (december 2021) , p. 23, ISSN 1423-0127 |
14 p, 2.9 MB |