Hepatitis B virus surface protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways.
The protein inhibitor of activated STAT1 (PIAS1) plays important roles in regulating virus-induced chronic hepatitis, but the interaction between hepatitis B virus (HBV) and hPIAS1 is not clear. Our aim was to verify if HBV encoding proteins enhance the transcription of hPIAS1 and which cis-elements and transcription factors were involved in the mechanism. In order to do, so a series of molecular biological methods, along with functional and histological studies, were performed. We found that the HBV surface protein (HBs) enhanced hPIAS1 transcription through the activities of TAL1, E47, myogenin (MYOG), and NFI, dependent on the activation of p38MAPK and ERK signaling pathways in vitro, which might contribute to the ineffectiveness of treatment in CHB patients. Furthermore, liver samples from patients with high HBsAg levels and HBV DNA displayed increased hPIAS1 expression and high levels of TAL1, E47, MYOG, and NFI, compared to those patients with low HBsAg levels and HBV DNA, and healthy controls. These findings suggest that the HBs protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways. It provides new potential targets for antiviral therapeutic strategies for controlling HBV-associated diseases.
Hongyan
H
Wang
Di
D
Wu
Xiaofeng
X
Wang
Guang
G
Chen
Yuanya
Y
Zhang
Weiming
W
Yan
Xiaoping
X
Luo
Meifang
M
Han
Qin
Q
Ning
D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D051839:NFI Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D058127:Transcription Factor 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D006514:Hepatitis B Surface Antigens; D020928:Mitogen-Activated Protein Kinases; D018008:Myogenin; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D050828:Protein Inhibitors of Activated STAT; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D058127:Transcription Factor 3; D014759:Viral Envelope Proteins; C503799:MYOG protein, human; C067143:TAL1 protein, human