Transforming growth factor-beta1 suppresses hepatitis B virus replication primarily through transcriptional inhibition of pregenomic RNA.
Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic cytokine with pivotal roles in the regulation of cellular functions and immune responses. In this study, we found that TGF-beta1 was able to effectively suppress hepatitis B virus (HBV) replication. In the presence of TGF-beta1, the level of viral replicative intermediates was dramatically decreased, both in actively dividing cells and in confluent cells. At the same time, the levels of viral transcripts, core protein, and nucleocapsid were significantly diminished by TGF-beta1 treatment. Interestingly, the inhibitory activity of TGF-beta1 was associated with preferential reduction of the level of pregenomic RNA compared with pre-C mRNA. Further analysis indicated that TGF-beta1 might exert its antiviral effect primarily through reducing expression of the HBV core protein by transcriptional regulation instead of posttranscriptional modification.


CONCLUSIONS
TGF-beta1 may play a dual role in HBV infection, in the suppression of immune responses against viral infection and in the direct inhibition of viral replication, resulting in minimization of liver damage in patients with chronic hepatitis.
Chou
Yu-Chi
YC
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Chen
Mong-Liang
ML
Hu
Cheng-Po
CP
Chen
Ya-Ling
YL
Chong
Chin-Liew
CL
Tsai
Yue-Lin
YL
Liu
Tzu-Ling
TL
Jeng
King-Song
KS
Chang
Chungming
C
D002460:Cell Line; D016679:Genome, Viral / Q000235:genetics; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D012367:RNA, Viral / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D053773:Transforming Growth Factor beta1