Cytidine deaminase APOBEC3B interacts with heterogeneous nuclear ribonucleoprotein K and suppresses hepatitis B virus expression

Zhang, Wei; Zhang, Xuzhao; Tian, Chunjuan; Wang, Tao; Sarkis, Phuong Thi Nguyen; Yong-min, Fang; Zheng, Shu; Yu, Xiao Fang; Xu, Rongzhen

doi:10.1111/j.1462-5822.2007.01020.x

Cited by 50 publications

(55 citation statements)

References 42 publications

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“…In experiments using the human A3B expression plasmid, no RT activity after cotransfection with the EIAV vector system was detectable in the cell supernatant. Since the expression of the EIAV vectors is driven by the cytomegalovirus promoter, this result would agree with a previous study of Zhang et al, where the authors concluded that human A3B is able to inhibit transcription of simian virus 40 and cytomegalovirus promoters (99). Again, CrFK cells were infected with vector stocks normalized for RT, and 3 days postinfection the cells were used to quantify intracellular luciferase activity.…”

Section: Vol 83 2009 Restriction Of Eiav By Apobec3 7551supporting

confidence: 90%

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Zielonka

Bravo²,

Marino

et al. 2009

J Virol

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The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equine and of several of the human and nonprimate A3 proteins against the Equine infectious anemia virus (EIAV), the Simian immunodeficiency virus (SIV), and the Adeno-associated virus type 2 (AAV-2). Hematopoietic cells of horses express at least five different A3s: A3Z1b, A3Z2a-Z2b, A3Z2c-Z2d, A3Z2e, and A3Z3, whereas circulating macrophages, the natural target of EIAV, express only part of the A3 repertoire. The five A3Z2 tandem copies arose after three consecutive, recent duplication events in the horse lineage, after the split between Equidae and Carnivora. The duplicated genes show different antiviral activities against different viruses: equine A3Z3 and A3Z2c-Z2d are potent inhibitors of EIAV while equine A3Z1b, A3Z2a-Z2b, A3Z2e showed only weak anti-EIAV activity. Equine A3Z1b and A3Z3 restricted AAV and all equine A3s, except A3Z1b, inhibited SIV. We hypothesize that the horse A3 genes are undergoing a process of subfunctionalization in their respective viral specificities, which might provide the evolutionary advantage for keeping five copies of the original gene.The Equine infectious anemia virus (EIAV) (family Retroviridae, genus Lentivirus) infects equids almost worldwide, causing a persistent infection characterized by recurring viremia, fever, thrombocytopenia, and wasting symptoms (40). EIAV infections are used as a model for natural immunologic control of lentivirus replication and virus persistence and as a test system to improve vaccines against lentiviruses (10,40,41,82). In vivo EIAV replicates predominantly in macrophages (77). Interaction with the equine lentiviral receptor 1 (ELR1) has been demonstrated to be responsible for EIAV internalization (96). There have been no reported cases of EIAV infections in humans, suggesting that it is an intrinsically safe virus and of interest for use in a clinical setting. Therefore, EIAV-based lentiviral vectors for human gene therapy were recently developed (1, 67, 68).In the last few years, two cellular proteins that inhibit many different retroviruses have been characterized: tripartite motif protein 5 alpha (TRIM5␣) and apolipoprotein B mRNAediting enzyme-catalytic polypeptide 3 (APOBEC3 [A3]) (for a review, see reference 92). With respect to TRIM5␣ proteins, both human and nonhuman primate TRIM5␣ orthologues can restrict infection by EIAV (26,72). The activity of equine TRIM5␣ on EIAV infection, however, has not been described so far. With respect to A3 proteins...

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Section: Vol 83 2009 Restriction Of Eiav By Apobec3 7551supporting

confidence: 90%

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Zielonka

Bravo²,

Marino

et al. 2009

J Virol

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“…Expression of a functional HIV-1 Vif protein counteracts the antiviral effects of A3G and A3F by recruiting them to the proteasome for degradation, thereby preventing their incorporation into viral particles (14, 24 -30). Although HIV-1 is the best studied A3 viral target, studies using A3 transfection systems have demonstrated that one or more human A3 proteins are also able to inhibit replication of other pathogenic human viruses, including HIV-2 (31), hepatitis B virus (32)(33)(34)(35), and parvoviruses (36,37).…”

Section: A3mentioning

confidence: 99%

Innate Immune Signaling Induces High Levels of TC-specific Deaminase Activity in Primary Monocyte-derived Cells through Expression of APOBEC3A Isoforms

Thielen

McNevin

McElrath

et al. 2010

Journal of Biological Chemistry

105

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In HIV-1-infected individuals, G-to-A hypermutation is found in HIV-1 DNA isolated from peripheral blood mononuclear cells (PBMCs). These mutations are thought to result from editing by one or more host enzymes in the APOBEC3 (A3) family of cytidine deaminases, which act on CC (APOBEC3G) and TC (other A3 proteins) dinucleotide motifs in DNA (edited cytidine underlined). Although many A3 proteins display high levels of deaminase activity in model systems, only low levels of A3 deaminase activity have been found in primary cells examined to date. In contrast, here we report high levels of deaminase activity at TC motifs when whole PBMCs or isolated primary monocyte-derived cells were treated with interferon-␣ (IFN␣) or IFN␣-inducing toll-like receptor ligands. Induction of TC-specific deaminase activity required new transcription and translation and correlated with the appearance of two APOBEC3A (A3A) isoforms. Knockdown of A3A in monocytes with siRNA abolished TC-specific deaminase activity, confirming that A3A isoforms are responsible for all TC-specific deaminase activity observed. Both A3A isoforms appear to be enzymatically active; moreover, our mutational studies raise the possibility that the smaller isoform results from internal translational initiation. In contrast to the high levels of TC-specific activity observed in IFN␣-treated monocytes, CC-specific activity remained low in PBMCs, suggesting that A3G deaminase activity is relatively inhibited, unlike that of A3A. Together, these findings suggest that deaminase activity of A3A isoforms in monocytes and macrophages may play an important role in host defense against viruses. A33 proteins are cytidine deaminases that are capable of inhibiting replication of retroviruses, DNA viruses, and retroelements (reviewed in Refs. 1-3). The seven A3 proteins in the human genome share a strong preference for deaminating cytidines that are in a CC or TC context in single-stranded DNA (edited cytidine underlined). Although APOBEC3G (A3G), the best understood A3 protein, acts preferentially on CC motifs, the six other human A3 proteins display varying degrees of preference for TC motifs (4 -13). Because other cytidine deaminases, such as activation-induced deaminase and APOBEC1, either display a strong preference for editing deoxycytidines in other dinucleotide contexts or act on TC motifs in RNA (4), mutations that arise in a CC or TC context in DNA constitute signatures of editing by A3 proteins.Much headway has been made in understanding how A3 proteins act on HIV-1 DNA, in part through transfection of A3 plasmids into human epithelium-derived cell lines, such as 293T or HeLa cells, which lack significant endogenous expression of most A3 proteins. From such studies, A3G and APOBEC3F (A3F) are known to be packaged into virus particles when the HIV-1 Vif protein is not expressed and to cause a substantial reduction in virus infectivity (5, 12, 14 -16). Reduced virus infectivity results in part from non-enzymatic inhibition of reverse transcription by A3G and A3F (17-2...

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“…It can also trigger other cells, such as macrophages and NK cells to secrete more cytokines, including IFN-α, forming a positive feedback loop (41). IFN-α is an important inducer of the A3 protein family, cellular DNA cytidine deaminases that function as inhibitors of viral replication (45). IFN-γ is produced by NK cells and at later stages by differentiated T cells (46).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-induced cytokine expression pattern in peripheral blood mononuclear cells in childhood obesity

Yue

Liu

2016

Molecular Medicine Reports

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Abstract. Obesity is characterized by the abnormal or excessive fat accumulation that may impair health and extensive increase in body mass index (BMI). Childhood obesity may occur due to disturbances in metabolic regulation, which lead to metabolic syndrome and other diseases. Peripheral blood suspended immune cells are responsible for immune surveillance. The aim of the present study was to map the inflammatory cytokine expression pattern of isolated peripheral blood mononuclear cells (PBMCs) following lipopolysaccharide (LPS) stress in vitro and clinical chemistry parameters in the plasma of subjects. PBMCs were isolated through density gradient ultracentrifugation of the blood from obese infants that would reflect the cytokine response. Isolated PBMCs were cultured in vitro in RPMI-1640 medium and stressed with 1 µg LPS in order to investigate the expression pattern of cytokines, such as interleukin (IL)-2, interferon (IFN)-γ, IFN-α, tumor necrosis factor-α and IL-6 using enzyme-linked immunosorbent assays and reverse transcription-quantitative polymerase chain reaction. Levels of NO, lipid levels, total protein, albumin, marker enzymes aspartate transaminase and alanine transaminase, malondialdehyde (MDA), and reduced glutathione in the plasma were detected. Reduction in the expression of the inflammatory cytokines in PBMCs, reduced protein and globulins, and altered MDA and GSH levels in the plasma were observed. Altered or compromised pro-inflammatory signals from PBMCs in vitro and the clinical chemistry parameters of the plasma suggested that there were compromised immunological responses in obese children compared with matched controls.

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Cytidine deaminase APOBEC3B interacts with heterogeneous nuclear ribonucleoprotein K and suppresses hepatitis B virus expression

Cited by 50 publications

References 42 publications

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Restriction of Equine Infectious Anemia Virus by Equine APOBEC3 Cytidine Deaminases

Innate Immune Signaling Induces High Levels of TC-specific Deaminase Activity in Primary Monocyte-derived Cells through Expression of APOBEC3A Isoforms

Lipopolysaccharide-induced cytokine expression pattern in peripheral blood mononuclear cells in childhood obesity

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