HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients
Por:
Brochado, O, Martinez, I, Berenguer, J, Medrano, L, Gonzalez-Garcia, J, Jimenez-Sousa, MA, Carrero, A, Hontanon, V, Navarro, J, Guardiola, JM, Fernandez-Rodriguez, A, Resino, S, Domingo P., Esteban, Herminia
Publicada:
30 mar 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.
Filiaciones:
Brochado, O:
Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Infecc Viral & Inmunidad, Campus Majadahonda,Carretera Majadahonda Pozuelo, Majadahonda Madrid 28220, Spain
Martinez, I:
Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Infecc Viral & Inmunidad, Campus Majadahonda,Carretera Majadahonda Pozuelo, Majadahonda Madrid 28220, Spain
Berenguer, J:
Hosp Gen Univ Gregorio Maranon, Unidad Enfermedades Infecciosas VIH, Madrid, Spain
Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
Medrano, L:
Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Infecc Viral & Inmunidad, Campus Majadahonda,Carretera Majadahonda Pozuelo, Majadahonda Madrid 28220, Spain
Gonzalez-Garcia, J:
Hosp Univ La Paz, Serv Med Interna, Unidad VIH, Madrid, Spain
Inst Invest Sanit La Paz IdiPAZABB, Madrid, Spain
Jimenez-Sousa, MA:
Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Infecc Viral & Inmunidad, Campus Majadahonda,Carretera Majadahonda Pozuelo, Majadahonda Madrid 28220, Spain
Carrero, A:
Hosp Gen Univ Gregorio Maranon, Unidad Enfermedades Infecciosas VIH, Madrid, Spain
Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
Hontanon, V:
Hosp Univ La Paz, Serv Med Interna, Unidad VIH, Madrid, Spain
Inst Invest Sanit La Paz IdiPAZABB, Madrid, Spain
Navarro, J:
Hosp Univ Vall dHebron, Serv Enfermedades Infecciosas, Barcelona, Spain
Inst Recerca Vall DHebron, Barcelona, Spain
Guardiola, JM:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Fernandez-Rodriguez, A:
Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Infecc Viral & Inmunidad, Campus Majadahonda,Carretera Majadahonda Pozuelo, Majadahonda Madrid 28220, Spain
Resino, S:
Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Infecc Viral & Inmunidad, Campus Majadahonda,Carretera Majadahonda Pozuelo, Majadahonda Madrid 28220, Spain
Domingo P.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Esteban, Herminia:
Fundación SEIMC-GESIDA, Madrid, Spain
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