Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:[Antiviral effect of antisense oligodeoxynucleotides complementary to hepatitis B virus X gene in vitro]. 1037 87

The pathogenesis of fatty liver disease remains largely unknown. Here, we assessed the importance of hepatic fat accumulation on the progression of hepatitis in zebrafish by liver specific expression of Hepatitis B virus X protein (HBx). Transgenic zebrafish lines, GBXs, which selectively express the GBx transgene (GFP-fused HBx gene) in liver, were established. GBX Liver phenotypes were evaluated by histopathology and molecular analysis of fatty acid (FA) metabolism-related genes expression. Most GBXs (66-81%) displayed obvious emaciation starting at 4 months old. Over 99% of the emaciated GBXs developed hepatic steatosis or steatohepatitis, which in turn led to liver hypoplasia. The liver histology of GBXs displayed steatosis, lobular inflammation, and balloon degeneration, similar to non-alcoholic steatohepatitis (NASH). Oil red O stain detected the accumulation of fatty droplets in GBXs. RT-PCR and Q-rt-PCR analysis revealed that GBx induced hepatic steatosis had significant increases in the expression of lipogenic genes, C/EBP-alpha, SREBP1, ChREBP and PPAR-gamma, which then activate key enzymes of the de novo FA synthesis, ACC1, FAS, SCD1, AGAPT, PAP and DGAT2. In addition, the steatohepatitic GBX liver progressed to liver degeneration and exhibited significant differential gene expression in apoptosis and stress. The GBX models exhibited both the genetic and functional factors involved in lipid accumulation and steatosis-associated liver injury. In addition, GBXs with transmissible NASH-like phenotypes provide a promising model for studying liver disease.
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PMID:Increase of hepatic fat accumulation by liver specific expression of Hepatitis B virus X protein in zebrafish. 2041 98

Hepatitis B virus (HBV) mRNA metabolism is dependent upon host proteins PAPD5 and PAPD7 (PAPD5/7). PAPD5/7 are cellular, non-canonical, poly(A) polymerases (PAP) whose main function is to oligoadenylate the 3' end of non-coding RNA (ncRNA) for exosome degradation. HBV seems to exploit these two ncRNA quality control factors for viral mRNA stabilization, rather than degradation. RG7834 is a small molecule compound that binds PAPD5/7 and inhibits HBV gene production in both tissue culture and animal study. We reported that RG7834 was able to destabilize multiple HBV mRNA species, ranging from the 3.5 kb pre-genomic/pre-core mRNAs to the 2.4/2.1 kb HBs mRNAs, except for the smallest 0.7 kb HBx mRNA. Compound induced HBV mRNA destabilization was initiated by a shortening of poly(A) tail followed by an accelerated degradation process in both the nucleus and cytoplasm. In cells expressing HBV mRNA, both PAPD5/7 were found to be physically associated with the viral RNA, and the polyadenylating activities of PAPD5/7 were susceptible to RG7834 repression in biochemical assay. Moreover, in PAPD5/7 double knockout cells, viral transcripts with regular length of poly(A) sequence could be initially synthesized but became shortened in hours suggesting that participation of PAPD5/7 in RNA 3' end processing, either during adenosine oligomerization or afterwards, is crucial for RNA stabilization.
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PMID:The dihydroquinolizinone compound RG7834 inhibits the polyadenylase function of PAPD5/7 and accelerates the degradation of matured HBV surface protein mRNA. 3304 85


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