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| Pàgina inicial > Articles > Articles publicats > HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients |
(Instituto de Salud Carlos III) (Instituto de Salud Carlos III) (Hospital General Universitario Gregorio Marañón) (Instituto de Salud Carlos III) (Hospital Universitario La Paz (Madrid)) (Instituto de Salud Carlos III) (Hospital Universitario La Paz (Madrid)) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Institut d'Investigació Biomèdica Sant Pau) (Instituto de Salud Carlos III) (Instituto de Salud Carlos III) (GESIDA Study Group) (GESIDA Study Group) (GESIDA Study Group) (Institut d'Investigació Biomèdica Sant Pau) (Hospital Universitari Vall d'Hebron) (GESIDA Study Group)| Data: | 2021 |
| Resum: | 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. |
| Ajuts: | 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). |
| Drets: | 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | HIV/HCV coinfection ; Gene expression ; Immune system ; HCV clearance ; Interferon therapy ; PBMCs |
| Publicat a: | Journal of Biomedical Science, Vol. 28 Núm. 1 (december 2021) , p. 23, ISSN 1423-0127 |
