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
ISSN: 10217770
Editorial
BMC, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, Taiwan
Tipo de documento: Article
Volumen: 28 Número: 1
Páginas:
WOS Id: 000635147800001
ID de PubMed: 33785040
imagen gold, Green Published

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