Journal article
Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release
Journal of virology, Vol.89(18), pp.9454-9464
09/01/2015
DOI: 10.1128/JVI.00955-15
PMCID: PMC4542372
PMID: 26157120
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 (P-corrected < 0.05) and a decrease in miR-494 (P-corrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P<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.
IMPORTANCE
MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe liver disease. We profiled plasma miRNAs in injection drug users before, during, and (in the people with resolution) after HCV infection. We discovered miRNA signatures of acute and persistent viremia and confirmed these findings two ways: (i) in a separate cohort of people with newly acquired HCV infection and (ii) in an HCV cell culture system. Our results demonstrate that acute HCV infection induces early changes in the abundance of specific plasma miRNAs that may affect the host response to HCV infection.
Details
- Title: Subtitle
- Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release
- Creators
- Ramy El-Diwany - Johns Hopkins UniversityLisa N. Wasilewski - Johns Hopkins UniversityKenneth W. Witwer - Johns Hopkins MedicineJustin R. Bailey - Johns Hopkins UniversityKimberly Page - University of New MexicoStuart C. Ray - Johns Hopkins UniversityAndrea L. Cox - Johns Hopkins MedicineDavid L. Thomas - Johns Hopkins MedicineAshwin Balagopal - Johns Hopkins Medicine
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.89(18), pp.9454-9464
- DOI
- 10.1128/JVI.00955-15
- PMID
- 26157120
- PMCID
- PMC4542372
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- Amer Soc Microbiology
- Number of pages
- 11
- Grant note
- T32AI007247 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01 DA 016078; U19 AI 088791; R37 DA 013806; 5R01 DA 031056; 2R01 DA 016017 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32GM007309 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R37DA013806 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission P30DK026743 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) UL1TR001449 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Language
- English
- Date published
- 09/01/2015
- Academic Unit
- Surgery
- Record Identifier
- 9984966746902771
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