Post-translational modification of delta antigen of hepatitis D virus

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, and Hepatitis Research Center, National Taiwan University Hospital, Taipei.
Current topics in microbiology and immunology (Impact Factor: 4.1). 02/2006; 307:91-112. DOI: 10.1007/3-540-29802-9_5
Source: PubMed


The hepatitis delta virus (HDV) genome has only one open reading frame, which encodes the viral small delta antigen. After RNA editing, the same open reading frame is extended 19 amino acids at the carboxyl terminus and encodes the large delta antigen. These two viral proteins escort the HDV genome through different cellular compartments for the complicated phases of replication, transcription and, eventually, the formation of progeny virions. To orchestrate these events, the delta antigens have to take distinct cues to traffic to the right compartments and make correct molecular contacts. In eukaryotes, post-translational modification (PTM) is a major mechanism of dictating the multiple functions of a single protein. Multiple PTMs, including phosphorylation, isoprenylation, acetylation, and methylation, have been identified on hepatitis delta antigens. In this chapter we review these PTMs and discuss their functions in regulating and coordinating the life cycle of HDV.

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    • "There are two HDAg isoforms: a small 24 kDa isoform, needed for replication, and a large 27 kDa variant which is essential for viral assembly and is generated by a post-transcriptional, RNA-specific adenosine deaminase (ADAR) mediated RNA-editing event [3] [4]. The balance between viral replication and assembly is conducted by the ratio of small and large HDAg and by different post-translational modifications such as prenylation, phosphorylation, methylation, acetylation, and sumoylation [5]. Moreover, HDV needs the surface proteins of the hepatitis B virus (HBV) to generate infectious viral particles and hence to complete the viral life-cycle [6]. "
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    ABSTRACT: Clinical studies have shown that hepatitis Delta virus (HDV) infection can persist for years and intrahepatic latency of large Delta antigen (HDAg) has been detected following liver transplantation. However, large HDAg arising via RNA-editing is associated with increasing amounts of non-infectious HDV quasi-species. This study investigated whether HDV could persist intrahepatically in the absence of HBV in vivo and whether infectious HDV could subsequently be released following HBV super-infection. Humanized mice were infected with HDV particles lacking HBV. To test for rescue of latent HDV infection 3 and 6 weeks HDV mono-infected mice were super-infected with HBV. Viral loads and cell toxicity were determined by qRT-PCR and immunohistochemistry. The presence of HDAg-positive human hepatocytes determined after 2, 3 and 6 weeks of HDV inoculation demonstrated establishment and maintenance of intrahepatic HDV mono-infection. Although intrahepatic amounts of large HDAg and edited HDV-RNA forms increased over time in HDV mono-infected livers, HBV super-infection led to prompt viremia development (up to 10(8) HDV-RNA and 10(7) HBV-DNA copies/ml) even after 6 weeks of latent mono-infection. Concurrently, the number of HDAg-positive human hepatocytes increased, demonstrating intrahepatic HDV spreading. The infectivity of the rescued HDV virions was verified by serial passage in naive chimeric mice. HDV mono-infection can persist intrahepatically for at least 6 weeks before being rescued by HBV. Conversion of a latent HDV infection to a productive HBV/HDV co-infection may contribute to HDV persistence even in patients with low HBV replication and in the setting of liver transplantation.
    Journal of Hepatology 11/2013; 60(3). DOI:10.1016/j.jhep.2013.11.010 · 11.34 Impact Factor
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    • "SDAg is required for genome replication while the LDAg is used for virion packaging [54]. Both antigens can target the nucleoli of human cells, although they also shuttle to other locations when posttranslationally modified [55–58]. LDAg is detectable at the nucleoli of transfected human hepatoma cells by using GFP as a reporter of gene expression (Figures 6(a)–6(c)). "
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    ABSTRACT: Nucleolar size and appearance correlate with ribosome biogenesis and cellular activity. The mechanisms underlying changes in nucleolar appearance and regulation of nucleolar size that occur during differentiation and cell cycle progression are not well understood. Caenorhabditis elegans provides a good model for studying these processes because of its small size and transparent body, well-characterized cell types and lineages, and because its cells display various sizes of nucleoli. This paper details the advantages of using C. elegans to investigate features of the nucleolus during the organism's development by following dynamic changes in fibrillarin (FIB-1) in the cells of early embryos and aged worms. This paper also illustrates the involvement of the ncl-1 gene and other possible candidate genes in nucleolar-size control. Lastly, we summarize the ribosomal proteins involved in life span and innate immunity, and those homologous genes that correspond to human disorders of ribosomopathy.
    BioMed Research International 04/2012; 2012:601274. DOI:10.1155/2012/601274 · 2.71 Impact Factor
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    • "However, since human and chimpanzee protein sequences are almost identical in most of the cases [11], the amino acid substitutions that may lead to Homo-Pan divergences in protein-protein interactions (PPIs) have remained elusive. Nevertheless, it is feasible to pinpoint species-specific post-translational modifications (PTMs), which are known to affect host-virus protein interactions [12,13] and can be altered by minor genetic changes such as single nucleotide substitutions or small insertions/deletions (indels). PTMs are pivotal to a wide range of biological processes, including signal transduction, protein targeting, receptor specificity, and PPIs [14]. "
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    ABSTRACT: The Human Immunodeficiency Virus type one (HIV-1) is the major causing pathogen of the Acquired Immune Deficiency Syndrome (AIDS). A large number of HIV-1-related studies are based on three non-human model animals: chimpanzee, rhesus macaque, and mouse. However, the differences in host-HIV-1 interactions between human and these model organisms have remained unexplored. Here we present CAPIH (Comparative Analysis of Protein Interactions for HIV-1), the first web-based interface to provide comparative information between human and the three model organisms in the context of host-HIV-1 protein interactions. CAPIH identifies genetic changes that occur in HIV-1-interacting host proteins. In a total of 1,370 orthologous protein sets, CAPIH identifies approximately 86,000 amino acid substitutions, approximately 21,000 insertions/deletions, and approximately 33,000 potential post-translational modifications that occur only in one of the four compared species. CAPIH also provides an interactive interface to display the host-HIV-1 protein interaction networks, the presence/absence of orthologous proteins in the model organisms in the networks, the genetic changes that occur in the protein nodes, and the functional domains and potential protein interaction hot sites that may be affected by the genetic changes. The CAPIH interface is freely accessible at CAPIH exemplifies that large divergences exist in disease-associated proteins between human and the model animals. Since all of the newly developed medications must be tested in model animals before entering clinical trials, it is advisable that comparative analyses be performed to ensure proper translations of animal-based studies. In the case of AIDS, the host-HIV-1 protein interactions apparently have differed to a great extent among the compared species. An integrated protein network comparison among the four species will probably shed new lights on AIDS studies.
    BMC Microbiology 09/2009; 9(1):164. DOI:10.1186/1471-2180-9-164 · 2.73 Impact Factor
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