Anti-hepatitis B virus activity and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein in vitro and in vivo.
OBJECTIVE
To evaluate the anti-hepatitis B virus (anti-HBV) effects and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein (rHSA-IFNalpha-2b) in vitro and in vivo.


METHODS
The inhibiting effects on HBV replication were examined in the HepG2 2.2.15 cell line and in ducks, and the expressions of signal transducers and transactivator 1 (STAT1), IFN-stimulated gene factor 3 (ISGF3) and 2',5'-oligoadenylate synthetase 1 (OAS1) were investigated by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.


RESULTS
In vitro,at concentrations from 0.075 to 1.2 nmol/l, rHSA-IFNalpha-2b inhibited the releases of extracellular hepatitis B surface antigen, hepatitis B e antigen and HBV DNA in a dose-dependent manner; rHSA- IFNalpha-2b also increased the levels of STAT1, ISGF3 and OAS1. In vivo, rHSA-IFNalpha-2b reduced the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin and duck hepatitis B virus (DHBV) DNA in the sera of DHBV-infected ducks.


CONCLUSIONS
We provide the first evidence that rHSA-IFNalpha-2b significantly inhibits HBV replication in HepG2 2.2.15 cells and in ducks, and that the antiviral effect of rHSA-IFNalpha-2b in vivo is more potent than that of IFNalpha-2b. The anti-HBV mechanism probably operates by triggering the JAK-STAT signaling pathway and increasing the expression of OAS1.
Bingfa
Xu
X
Institute of Clinical Pharmacology, Anhui Medical University, Hefei, PR China.
Qinglin
Fan
F
Hui
Huang
H
Canjun
Wang
W
Wei
Wei
W
Lihua
Song
S
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases; D001663:Bilirubin / Q000097:blood; D002460:Cell Line; D004247:DNA / Q000097:blood; D004279:DNA, Viral; D004353:Drug Evaluation, Preclinical; D004372:Ducks; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D050832:Interferon-Stimulated Gene Factor 3; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D012709:Serum Albumin; C543152:human serum albumin-interferon-alpha-2b fusion protein; D004247:DNA; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D015088:2',5'-Oligoadenylate Synthetase; D001663:Bilirubin; D000075462:Serum Albumin, Human