Dataset Information

Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study.

ABSTRACT: Exosomes seem to play an important role in hepatits C virus (HCV) and hepatitis E virus (HEV) infection by shielding their cargo from the host immune responses, with microRNAs being key exosomal components. Little is known about their involvement in a mixed HCV/HEV infection or at the early stages of infection, such as in asymptomatic blood donors (BDs). To obtain preliminary data, we have compared the exosomal microRNA expression profiles in four each of HCV RNA-positive, HEV RNA-positive and negative blood donors and four patients, one of whom was a rare patient with HCV/HEV co-infection. Exosomes were purified from sera by a combination of a precipitation and density gradient centrifugation and exosomal microRNA was analysed using Taqman array cards. Out of 33 deregulated miRNAs, miR-885-5p and miR-365 were upregulated in HCV BDs, miR-627-5p was downregulated in HCV BD and miR-221 was downregulated in HCV patients and BDs. In HEV infection, miR-526b appeared specifically downregulated. Six miRNAs (miR-628-3p, miR-194, miR-151-3p, miR-512-3p, miR-335 and miR-590) indicated a potential involvement in both infections. First time preliminary data on pre- and post-antiviral treatment exosomal microRNA profiles of the HEV/HCV co-infected patient revealed a pool of 77 upregulated and 43 downregulated miRNAs to be further investigated for their potential roles in these viral infections.

SUBMITTER: McGowan K

PROVIDER: S-EPMC7472156 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study.

McGowan Karen K Simpson Kenneth J KJ Petrik Juraj J

Viruses 20200730 8

Exosomes seem to play an important role in hepatits C virus (HCV) and hepatitis E virus (HEV) infection by shielding their cargo from the host immune responses, with microRNAs being key exosomal components. Little is known about their involvement in a mixed HCV/HEV infection or at the early stages of infection, such as in asymptomatic blood donors (BDs). To obtain preliminary data, we have compared the exosomal microRNA expression profiles in four each of HCV RNA-positive, HEV RNA-positive and n ...[more]

PMID: 32751663

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Project description:In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro-fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR-101, miR-122, miR-155, miR-192, miR-200c, miR-338, and miR-532 was determined by quantitative real-time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV-infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post-LT. None of the patients was treated with direct-acting anti-HCV drugs. All co-infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR-101 (p = .03), miR-122 (p = .012), and miR-192 (p = .038) were significantly downregulated in HCV/HIV co-infected and HCV mono-infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co-infected ones. Moreover, in co-infected recipients but not in mono-infected ones, miR-101 inversely correlated with the peripheral HCV-RNA levels (r = .41, p = .04) and miR-122 inversely correlated with peripheral HCV-RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02). In conclusion, as early as 6 months after LT, the presence of HIV-HCV co-infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.

Project description:BackgroundHearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.MethodsWe conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.ResultsA total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.ConclusionsIn patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

Dataset Information

Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study.

Publications

Expression Profiles of Exosomal MicroRNAs from HEV- and HCV-Infected Blood Donors and Patients: A Pilot Study.

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