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)

Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanism by which AID triggers SHM and CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV-replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID's RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV.
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PMID:RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase. 2334 89

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Various risk factors are involved in hepatocarcinogenesis. Among them, chronic inflammation, including chronic hepatitis and cirrhosis mainly caused by hepatitis B virus and/or hepatitis C virus infection, plays an important role in HCC development. On the other hand, comprehensive genetic analyses of HCC using whole genome and exome sequencing revealed that cancer cells possess a large number of somatic mutations, suggesting that a wide variety of genetic alterations and the resultant dysregulated molecular pathways contribute to the development of HCC. Activation-induced cytidine deaminase (AID) is a nucleotide-editing enzyme, and aberrant expression of AID induced by inflammatory responses contributes to hepatocarcinogenesis via the accumulation of genetic alterations in various tumor-related genes. Constitutive expression of AID in hepatocyte-lineage cells provides novel mouse models that recapitulate the tumorigenesis of human HCC through stepwise accumulation of genetic alterations.
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PMID:Novel mouse models of hepatocarcinogenesis with stepwise accumulation of genetic alterations. 2428 Oct 20

Activation-induced cytidine deaminase (AID) not only promotes immune diversity by initiating somatic hypermutation and class switch recombination in immunoglobulin genes but also provokes genomic instability by introducing translocations and mutations into non-immunoglobulin genes. To test whether AID is essential for virus-induced tumor development, we used two transgenic tumor models: mice expressing hepatitis C virus (HCV) core proteins (HCV-Tg), driven by the hepatitis B virus promoter, and mice expressing human papillomavirus type 8 proteins (HPV8-Tg), driven by the Keratin 14 promoter. Both strains were analyzed in the absence and presence of AID by crossing each with AID (-/-) mice. There was no difference in the liver tumor frequency between the HCV-Tg/AID (+/+) and HCV-Tg/AID (-/-) mice at 20 months of age although the AID (+/+) mice showed more severe histological findings and increased cytokine expression. Furthermore, a low level of AID transcript was detected in the HCV-Tg/AID (+/+) liver tissue that was not derived from hepatocytes themselves but from intra-hepatic immune cells. Although AID may not be the direct cause of HCV-induced oncogenesis, AID expressed in B cells, not in hepatocytes, may prolong steatosis and cause increased lymphocyte infiltration into HCV core protein-induced liver lesions. Similarly, there was no difference in the time course of skin tumor development between the HPV8-Tg/AID (-/-) and HPV8-Tg/AID (+/+) groups. In conclusion, AID does not appear to be required for tumor development in the two virus-induced tumor mouse models tested although AID expressed in infiltrating B cells may promote inflammatory reactions in HCV core protein-induced liver pathogenesis.
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PMID:Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models. 2456 64

Activation-induced cytidine deaminase (AID), a member of the APOBEC family that induces antibody diversification, has been shown to inhibit the replication of hepatitis B virus, Kaposi's sarcoma-associated herpesvirus, and retro-transposons. However, whether AID can inhibit human immunodeficiency virus 1 (HIV-1) replication remains unclear. Here, we report that AID impairs the synthesis of HIV-1 components by interacting with the complex of Tat. This interaction recruits the RNA exosome to degrade the nascent HIV-1 transcript. AID also targets the HIV-1-integrated genome via the Tat-P-TEFb-TAR complex. Thus, we propose a novel function for AID as an adaptor protein that represses viral transcription. Our findings provide insights into developing anti-HIV therapeutics and understanding how host cells restrict integrated virus replication.
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PMID:AID recruits the RNA exosome to degrade HIV-1 nascent transcripts through interaction with the Tat-P-TEFb-TAR RNP complex. 2926