Acute hepatitis C virus infection induces consistent changes in circulating MicroRNAs that are associated with nonlytic hepatocyte release

Ramy El-Diwany, Lisa N. Wasilewski, Kenneth W. Witwer, Justin R. Bailey, Kimberly Page, Stuart C. Ray, Andrea L. Cox, David L. Thomas, Ashwin Balagopal

Research output: Contribution to journalArticle

Abstract

Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P< 0.01) and miR-885-5p (Pcorrected<0.05) and a decrease in miR-494 (Pcorrected<0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (PP<0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P<0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans.

Original languageEnglish (US)
Pages (from-to)9454-9464
Number of pages11
JournalJournal of virology
Volume89
Issue number18
DOIs
StatePublished - Jan 1 2015

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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