Different HCV exposure drives specific miRNA profile in PBMCS of HIV patients

18 Pág. Departamento de ​Mejora Genética Animal
Micro RNAs (miRNAs) are essential players in HIV and HCV infections, as both viruses modulate cellular miRNAs and interact with the miRNA-mediated host response. We aim to analyze the miRNA profile of HIV patients with different exposure to HCV to explore specific signatures in the miRNA profile of PBMCs for each type of infection. We massively sequenced small RNAs of PBMCs from 117 HIV+ infected patients: 45 HIV+ patients chronically infected with HCV (HIV/HCV+), 36 HIV+ that spontaneously clarified HCV after acute infection (HIV/HCV-) and 36 HIV+ patients without previous HCV infection (HIV). Thirty-two healthy patients were used as healthy controls (HC). Differential expression analysis showed significantly differentially expressed (SDE) miRNAs in HIV/HCV+ (n = 153), HIV/HCV- (n = 169) and HIV (n = 153) patients. We found putative dysregulated pathways, such as infectious-related and PI3K signaling pathways, common in all contrasts. Specifically, putatively targeted genes involved in antifolate resistance (HIV/HV+), cancer-related pathways (HIV/HCV-) and HIF-signaling (HIV) were identified, among others. Our findings revealed that HCV strongly influences the expression profile of PBMCs from HIV patients through the disruption of its miRNome. Thus, different HCV exposure can be identified by specific miRNA signatures in PBMCs.
This work has been supported by grants from Institute of Health Carlos III, [PI15CIII/00031 and PI18CIII/00020/ to AFR and VB] and the Foundation Universidad Alfonso X el Sabio-Santander [grant number 1.010.932 to AFR] and the Spanish AIDS Research Network (RD16CIII/0002/0002), and Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044). AFR is supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) [CP14/CIII/00010 and CPII20CIII/0001]