Kinetics of miR-122 expression in the liver during acute HCV infection

• Published in: PloS one Vol. 8; no. 10; p. e76501
• Main Authors: Choi, Youkyung, Dienes, Hans-Peter, Krawczynski, Kris
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04-10-2013; Public Library of Science (PLoS)
• Subjects: Alanine; Alanine transaminase; Analysis; Animals; Caenorhabditis elegans - genetics; Chimpanzees; Cloning; Correlation; Destruction; Disease control; Gene expression; Gene Expression Regulation - drug effects; Genomes; Genotypes; Health aspects; Hepacivirus; Hepatitis; Hepatitis C; Hepatitis C - genetics; Hepatitis C - virology; Hepatitis C virus; Infection; Infections; Inoculation; Interferon; Interferon Type I - pharmacology; Kinases; Kinetics; Laboratory animals; Liver; Liver - drug effects; Liver - metabolism; Liver - virology; Medical laboratories; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Nutrition research; Pan troglodytes; Pan troglodytes - genetics; Pan troglodytes - virology; Proteins; Replication; Ribonucleic acid; RNA; Studies; Viral infections; Viral Load; Viruses; Atlanta Georgia; United States > US; Georgia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076501

The relationships among micro RNA-122 (miR-122) expression in the liver, hepatitis C virus (HCV) replication and hepatic damage were analyzed in three chimpanzees observed for 180 days after inoculation with HCV genotype 1a. Levels of miR-122 in the liver and serum were measured by real-time RT PCR in serial liver biopsies and serum samples. Hepatic miR-122 levels were normalized separately for each of three chimpanzees with small RNAs and microRNAs that are endogenous to the liver and are stably expressed. Two- to 4-fold rise in hepatic miR-122 levels was observed at the onset of HCV infection (the first 4 weeks) when HCV titers in the liver and serum increased rapidly in all three chimpanzees in concordance with in vitro data indicating the miR-122 significance for HCV replication. Between 10 to 14 weeks after inoculation, when hepatic and serum HCV RNA titers exceeded 3 logs and alanine aminotransferase (ALT) activity was elevated, hepatic miR-122 levels were in decline. Cumulative data derived from all three chimpanzees from 180 days of observation documented an inverse (negative) correlation between hepatic miR-122 and HCV RNA in the liver and serum and positive correlation between level of serum miR-122 and HCV replication. Subsequent rise of miR-122 level during HCV clearance and ALT normalization suggested a tri-phasic occurrence of the relationship among hepatic miR-122 expression, HCV replication and hepatic destruction, which was the most apparent in one chimpanzee but less evident in two other animals. In vivo kinetics of hepatic and serum miR-122, HCV replication and hepatic destruction reflects complexities of the virus-host interaction during the acute phase of HCV infection.