- 作者: Óscar Brochado, Isidoro Martínez, Juan Berenguer, Luz Medrano, Juan González-García, María Ángeles Jiménez-Sousa, Ana Carrero, Víctor Hontañón, Jordi Navarro, Josep M. Guardiola, Amanda Fernández-Rodríguez and Salvador Resino
- 作者服務機構: 1.Unidad de Infección Viral E Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, 28220, MajadahondaMadrid, Spain 2.Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain 3.Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain 4.Hospital Santa Creu I Sant Pau, Barcelona, Spain 5.Servicio de Enfermedades Infecciosas, Hospital Universitari Vall D’Hebron, Barcelona, Spain 6.Institut de Recerca Vall D’Hebron, Barcelona, Spain 7.Unidad de VIH, Servicio de Medicina Interna, Hospital Universitario “La Paz”, Madrid, Spain 8.Instituto de Investigacion Sanitaria La Paz (IdiPAZ), Madrid, Spain
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: HIV/HCV coinfection, Gene expression, Immune system, HCV clearance, Interferon therapy, PBMCs