Adenoviral-vector mediated transfer of HBV-targeted ribonuclease can inhibit HBV replication in vivo.
Hepatitis B virus (HBV)-targeted ribonuclease (HBV-TR) is a fused protein of HBV core protein and a ribonuclease, human eosinophil-derived neurotoxin (hEDN). Our previous results showed that HBV-TR could effectively inhibit HBV replication in vitro. To test whether HBV-TR can inhibit HBV replication in vivo, we constructed a recombinant adenoviral vector expressing HBV-TR (Ad-TR) and used it to treat HBV-transgenic mice. Immunohistochemical staining showed that TR was expressed at varied levels in different tissues of Ad-TR-treated mice. Serum HBsAg concentration was decreased by 64.8% for the Ad-TR-treated mice compared with empty adenoviral vector-treated control mice. The amount of HBV-DNA in the livers of the Ad-TR-treated mice was 0.74 x 10(7) copies/mug of genomic DNA while the amount of HBV-DNA in the livers of the empty adenoviral vector-treated control mice was 2.86 x 10(7) copies/mug of genomic DNA. Serum HBV-DNA of Ad-TR-treated mice was also decreased by 71.4% compared with empty adenoviral vector-treated control mice. In addition, for some Ad-TR-treated mice, the expression of HBsAg in the liver cells turned negative. No discernible adverse effects were observed for Ad-TR-treated mice. Taken together, our results indicated that adenovirus mediated transfer of HBV-TR can inhibit HBV replication in vivo.
Zhao
Ya
Y
Department of Medical Microbiology and Parasitology, Fourth Military Medical University, 17 Changlexi Road, Xi'an, Shaanxi 710032, China.
Li
Yinghui
Y
Liu
Jun
J
Liu
Zhongxiang
Z
Huang
Yuxiao
Y
Lei
Junchuan
J
Li
Shumei
S
Xue
Caifang
C
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D047208:Eosinophil-Derived Neurotoxin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014018:Tissue Distribution; D014758:Viral Core Proteins / Q000235:genetics; D014779:Virus Replication
D000914:Antibodies, Viral; D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; D047208:Eosinophil-Derived Neurotoxin