[Antiviral effect of antisense oligodeoxynucleotides complementary to hepatitis B virus X gene in vitro].
It has been reported that the products of the human hepatitis B virus (HBV) X genes can transactivate a variety of viral and host promoters including the X, core, pre S2/S and pre S1 promoter. In order to investigate their antiviral effect in cell culture, three pieces of antisense phosphorothioate oligodeoxynucleotides (ASON) complementary to HBV X genes 1510-1530, 1555-1581, 1768-1791 regions were synthesized. The specificity of the inhibitory effect of the ASON was determined by using 2, 2, 15 cells by ELISA, PAP-ELISA and in situ hybridization to detect HBsAg, HBeAg, HBxAg and HBV DNA. The results showed that these ASON could inhibit the expression of HBxAg, as well as HBsAg and HBeAg, with the inhibitary rates of 78.07%, 80.65% and 62.76% respectively. In situ hybridization results indicated that HBV DNA replication can also be inhibited. The decrease in virus production and the ammount of HBV DNA were dose and time dependent. The mechanism of action may be due to the inhibition of HBxAg by sequences specific to ASON, and then the decrease of its transactivating effect for HBV DNA promoter.
Feng
Z
Z
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an.
Zhou
Y
Y
Yao
Z
Z
D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D015534:Trans-Activators / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D020319:Oligodeoxyribonucleotides, Antisense; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein