HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Journal of biomedical science - 28(2021), 1 vom: 30. März, Seite 23 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Brochado, Óscar [VerfasserIn] |
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| Links: |
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| Themen: |
9008-11-1 |
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| Anmerkungen: |
Date Completed 13.09.2021 Date Revised 13.09.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12929-021-00718-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323407773 |
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| 100 | 1 | |a Brochado, Óscar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 13.09.2021 | ||
| 500 | |a Date Revised 13.09.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gene expression | |
| 650 | 4 | |a HCV clearance | |
| 650 | 4 | |a HIV/HCV coinfection | |
| 650 | 4 | |a Immune system | |
| 650 | 4 | |a Interferon therapy | |
| 650 | 4 | |a PBMCs | |
| 650 | 7 | |a Interferons |2 NLM | |
| 650 | 7 | |a 9008-11-1 |2 NLM | |
| 700 | 1 | |a Martínez, Isidoro |e verfasserin |4 aut | |
| 700 | 1 | |a Berenguer, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Medrano, Luz |e verfasserin |4 aut | |
| 700 | 1 | |a González-García, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Jiménez-Sousa, María Ángeles |e verfasserin |4 aut | |
| 700 | 1 | |a Carrero, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Hontañón, Víctor |e verfasserin |4 aut | |
| 700 | 1 | |a Navarro, Jordi |e verfasserin |4 aut | |
| 700 | 1 | |a Guardiola, Josep M |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Rodríguez, Amanda |e verfasserin |4 aut | |
| 700 | 1 | |a Resino, Salvador |e verfasserin |4 aut | |
| 700 | 0 | |a GESIDA Study Group |e verfasserin |4 aut | |
| 700 | 1 | |a Carrero, A |e investigator |4 oth | |
| 700 | 1 | |a Miralles, P |e investigator |4 oth | |
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| 700 | 1 | |a Padilla, B |e investigator |4 oth | |
| 700 | 1 | |a Aldamiz-Echevarría, T |e investigator |4 oth | |
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| 700 | 1 | |a Van den Eynde, E |e investigator |4 oth | |
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| 700 | 1 | |a Ribera, E |e investigator |4 oth | |
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| 700 | 1 | |a Casado, J L |e investigator |4 oth | |
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