HBV replication is significantly reduced by IL-6.
Interleukin-6 (IL-6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV) replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA) in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-alpha/beta and IFN-gamma did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection.
Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan, ROC. d49002010@ym.edu.tw
Tzer-Min
TM
Kuo
Cheng-Po
CP
Hu
Ya-Ling
YL
Chen
Ming-Hsiang
MH
Hong
King-Song
KS
Jeng
Chun-Chin T
CC
Liang
Mong-Liang
ML
Chen
Chungming
C
Chang
D002478:Cells, Cultured; D016679:Genome, Viral; D006509:Hepatitis B / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D019251:Nucleocapsid / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D015850:Interleukin-6