Chronic hepatitis E virus infection is specifically associated with an interferon-related transcriptional program

J Infect Dis. 2013 Jan 1;207(1):125-32. doi: 10.1093/infdis/jis632. Epub 2012 Oct 16.

Abstract

Background: Hepatitis E virus (HEV) is a new causative agent of chronic hepatitis in solid organ transplant recipients. Clinical studies suggest that the occurrence and persistence of chronic HEV infection are related to the immunological status of patients.

Methods: We used whole-genome microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to compare the transcriptional profiles of whole blood from 8 kidney transplant recipients with chronic HEV infection and 8 matched kidney transplant recipients without HEV infection.

Results: We found that 30 genes in HEV-infected patients were upregulated, compared with those in control patients, as determined by microarray analysis. In contrast, no genes were downregulated. The 30 upregulated genes included 25 interferon-stimulated genes. Increased expression of the genes that encode IFIT1, IFI44L, RSAD2, EPSTI1, and ISG15 was confirmed by qRT-PCR. Interestingly, the expression levels of these genes were associated with the persistence of HEV infection.

Conclusions: Increased expression of interferon-stimulated genes may favor the persistence of an HEV infection. Whether the expression of interferon-stimulated genes is a marker of ongoing viremia or independent prognostic marker of HEV clearance needs further investigations.

Clinical trials registration: NCT01090232.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • France / epidemiology
  • Gene Expression Profiling
  • Gene Expression Regulation, Viral
  • Hepatitis Antibodies / blood
  • Hepatitis E / epidemiology
  • Hepatitis E / genetics
  • Hepatitis E / immunology*
  • Hepatitis E / virology
  • Hepatitis E virus / genetics
  • Hepatitis E virus / immunology*
  • Hepatitis, Chronic / epidemiology
  • Hepatitis, Chronic / genetics
  • Hepatitis, Chronic / immunology*
  • Hepatitis, Chronic / virology
  • Humans
  • Interferons / genetics*
  • Interferons / immunology
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / immunology
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Postoperative Complications / epidemiology*
  • Postoperative Complications / immunology
  • Postoperative Complications / virology
  • Prospective Studies
  • RNA, Viral / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Hepatitis Antibodies
  • RNA, Viral
  • Interferons

Associated data

  • ClinicalTrials.gov/NCT01090232