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Hepatitis Delta Virus: A Peculiar Virus

DOI: 10.1155/2013/560105

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The hepatitis delta virus (HDV) is distributed worldwide and related to the most severe form of viral hepatitis. HDV is a satellite RNA virus dependent on hepatitis B surface antigens to assemble its envelope and thus form new virions and propagate infection. HDV has a small 1.7?Kb genome making it the smallest known human virus. This deceivingly simple virus has unique biological features and many aspects of its life cycle remain elusive. The present review endeavors to gather the available information on HDV epidemiology and clinical features as well as HDV biology. 1. Introduction In 1977, a novel antigen was found in the nucleus of hepatocytes from patients with a more severe form of hepatitis B. It was first thought to be a previously unknown marker of hepatitis B virus (HBV). Only later, it was found that the then called delta antigen was not part of HBV but of a separate defective virus that requires the presence of HBV for infection. The newfound virus was designated hepatitis delta virus (HDV) and, by 1986, its RNA genome was cloned and sequenced (reviewed by [1]). This peculiar virus has been classified as the only member of the genus Deltavirus due to its uniqueness [2]. The HDV virion is a hybrid particle, composed of the delta antigen and HDV RNA enclosed by the surface antigens of HBV (HBsAgs). HDV has the smallest RNA genome of all known animal viruses. However, it is comparable, although larger, to viroid RNAs, pathogenic agents of higher plants. 2. Epidemiology HDV infection is distributed worldwide, although not uniformly, and it is estimated that 5% of HBsAgs carriers are also infected with HDV, which signifies that there might be between 15 and 20 million HDV-infected individuals [3]. This is a very rough number because it lacks data from areas where HBV is highly prevalent and HDV is poorly studied. HDV is highly endemic in Mediterranean countries, the Middle East, northern parts of South America, and Central Africa [4]. HDV also has high prevalence in Turkey [5], Central Asia [6], and the Amazonian region of Western Brazil [7]. In Southern Europe, HDV infection has been highly prevalent, with studies from the 1980s and 1990s showing that the incidence of HDV in HBsAgs positive individuals was higher than 20% [8]. With the implementation of HBV vaccination programs in the 1980s, HDV prevalence considerably decreased to 5–10% by the late 1990s [9]. However, in the beginning of the XXI century, the number of HDV-infected HBsAgs carriers in Europe increased to 8–12% [9, 10]. This increase has been attributed to immigration of

References

[1]  M. Rizzetto, “Hepatitis D: thirty years after,” Journal of Hepatology, vol. 50, no. 5, pp. 1043–1050, 2009.
[2]  F. A. Murphy, “Virus taxonomy,” in Fields Virology, B. N. Fields, D. M. Knipe, and P. M. Howley, Eds., vol. 2, pp. 15–57, 3rd edition, 1996.
[3]  M. Rizzetto and A. Ciancio, “Epidemiology of hepatitis D,” Seminars in Liver Disease, vol. 32, no. 3, pp. 211–219, 2012.
[4]  N. Radjef, E. Gordien, V. Ivaniushina et al., “Molecular phylogenetic analyses indicate a wide and ancient radiation of african hepatitis delta virus, suggesting a Deltavirus genus of at least seven major clades,” Journal of Virology, vol. 78, no. 5, pp. 2537–2544, 2004.
[5]  I. H. Bahcecioglu, C. Aygun, N. Gozel, O. K. Poyrazoglu, Y. Bulut, and M. Yalniz, “Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients in eastern Turkey: still a serious problem to consider,” Journal of Viral Hepatitis, vol. 18, no. 7, pp. 518–524, 2011.
[6]  B. Tsatsralt-Od, M. Takahashi, T. Nishizawa, K. Endo, J. Inoue, and H. Okamoto, “High prevalence of dual or triple infection of hepatitis B, C, and delta viruses among patients with chronic liver disease in Mongolia,” Journal of Medical Virology, vol. 77, no. 4, pp. 491–499, 2005.
[7]  R. Paraná, A. Kay, F. Molinet et al., “HDV genotypes in the Western Brazilian Amazon region: a preliminary report,” American Journal of Tropical Medicine and Hygiene, vol. 75, no. 3, pp. 475–479, 2006.
[8]  P. Farci, “Delta hepatitis: an update,” Journal of Hepatology, vol. 39, no. 1, pp. S212–S219, 2003.
[9]  G. B. Gaeta, T. Stroffolini, A. Smedile, G. Niro, and A. Mele, “Hepatitis delta in Europe: vanishing or refreshing?” Hepatology, vol. 46, no. 4, pp. 1312–1313, 2007.
[10]  H. Wedemeyer, B. Heidrich, and M. P. Manns, “Hepatitis D virus infection—not a vanishing disease in Europe,” Hepatology, vol. 45, no. 5, pp. 1331–1332, 2007.
[11]  R. G. Gish, D. H. Yi, S. Kane, M. Clask, M. Mangahas, et al., “Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California,” Journal of Gastroenterology and Hepatology, vol. 28, no. 9, pp. 1521–1525, 2013.
[12]  F. Le Gal, E. Gault, M.-P. Ripault et al., “Eighth major clade for hepatitis delta virus,” Emerging Infectious Diseases, vol. 12, no. 9, pp. 1447–1450, 2006.
[13]  C.-W. Su, Y.-H. Huang, T.-I. Huo et al., “Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients,” Gastroenterology, vol. 130, no. 6, pp. 1625–1635, 2006.
[14]  S. A. Hughes, H. Wedemeyer, and P. M. Harrison, “Hepatitis delta virus,” The Lancet, vol. 378, no. 9785, pp. 73–85, 2011.
[15]  M. S. Gomes-Gouvêa, M. C. P. Soares, G. Bensabath et al., “Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region,” Journal of General Virology, vol. 90, no. 11, pp. 2638–2643, 2009.
[16]  J.-C. Wu, T.-Y. Chiang, and I.-J. Sheen, “Characterization and phylogenetic analysis of a novel hepatitis D virus strain discovered by restriction fragment length polymorphism analysis,” Journal of General Virology, vol. 79, no. 5, pp. 1105–1113, 1998.
[17]  H. Watanabe, K. Nagayama, N. Enomoto et al., “Chronic hepatitis delta virus infection with genotype IIb variant is correlated with progressive liver disease,” Journal of General Virology, vol. 84, no. 12, pp. 3275–3289, 2003.
[18]  A. Ottobrelli, A. Marzano, A. Smedile et al., “Patterns of hepatitis delta virus reinfection and disease in liver transplantation,” Gastroenterology, vol. 101, no. 6, pp. 1649–1655, 1991.
[19]  S. Govindarajan, K. P. Chin, A. G. Redeker, and R. L. Peters, “Fulminant B viral hepatitis: role of delta agent,” Gastroenterology, vol. 86, no. 6, pp. 1417–1420, 1984.
[20]  P. Farci and G. Niro, “Clinical features of hepatitis D,” Seminars in Liver Disease, vol. 32, pp. 228–236, 2012.
[21]  A. Smedile, G. Verme, and A. Cargnel, “Influence of delta infection on severity of hepatitis B,” The Lancet, vol. 2, no. 8305, pp. 945–947, 1982.
[22]  A. Smedile, P. Dentico, and A. Zanetti, “Infection with the delta (δ) agent in chronic HBsAg carriers,” Gastroenterology, vol. 81, no. 6, pp. 992–997, 1981.
[23]  P. Farci, P. Karayiannis, M. E. Lai et al., “Acute and chronic hepatitis delta virus infection: direct or indirect effect on hepatitis B virus replication?” Journal of Medical Virology, vol. 26, no. 3, pp. 279–288, 1988.
[24]  G. Fattovich, S. Boscaro, and F. Noventa, “Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B,” Journal of Infectious Diseases, vol. 155, no. 5, pp. 931–935, 1987.
[25]  G. Saracco, F. Rosina, M. R. Brunetto et al., “Rapidly progressive HBsAg-positive hepatitis in Italy. The role of hepatitis delta virus infection,” Journal of Hepatology, vol. 5, no. 3, pp. 274–281, 1987.
[26]  G. Fattovich, G. Giustina, E. Christensen et al., “Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B,” Gut, vol. 46, no. 3, pp. 420–426, 2000.
[27]  T. J. S. Cross, P. Rizzi, M. Horner et al., “The increasing prevalence of hepatitis delta virus (HDV) infection in South London,” Journal of Medical Virology, vol. 80, no. 2, pp. 277–282, 2008.
[28]  C.-J. Chen, H.-I. Yang, J. Su et al., “Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA Level,” Journal of the American Medical Association, vol. 295, no. 1, pp. 65–73, 2006.
[29]  H. Wedemeyer and M. P. Manns, “Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead,” Nature Reviews Gastroenterology and Hepatology, vol. 7, no. 1, pp. 31–40, 2010.
[30]  K. Zachou, C. Yurdayin, H. Dienes, G. Dalekos, A. Erhardt, et al., “Significance of HDV-RNA and HBsAg levels in delta hepatitis: first data of the Hep-Net/international HDV intervention trial,” Journal of Hepatology, vol. 44, Supplement 2, p. S178, 2006.
[31]  A. Olivero and A. Smedile, “Hepatitis delta virus diagnosis,” Seminars in Liver Disease, vol. 32, pp. 220–227, 2012.
[32]  C. Scholtes, V. Icard, M. Amiri, P. Chevallier-Queyron, M. A. Trabaud, et al., “Standardized one-step real-time reverse transcription-PCR assay for universal detection and quantification of hepatitis delta virus from clinical samples in the presence of a heterologous internal-control RNA,” Journal of Clinical Microbiology, vol. 50, pp. 2126–2128, 2012.
[33]  R. B. Ferns, E. Nastouli, and J. A. Garson, “Quantitation of hepatitis delta virus using a single-step internally controlled real-time RT-qPCR and a full-length genomic RNA calibration standard,” Journal of Virological Methods, vol. 179, no. 1, pp. 189–194, 2012.
[34]  H. Wedemeyer, C. Yurdaydìn, G. N. Dalekos et al., “Peginterferon plus adefovir versus either drug alone for hepatitis delta,” The New England Journal of Medicine, vol. 364, no. 4, pp. 322–331, 2011.
[35]  G. A. Niro, F. Rosina, and M. Rizzetto, “Treatment of hepatitis D,” Journal of Viral Hepatitis, vol. 12, no. 1, pp. 2–9, 2005.
[36]  H. Wedemeyer, C. Yurdaydin, G. Dalekos, A. Erhardt, Y. Cakaloglu, et al., “[4] 72 week data of the HIDIT-1 trial: a multicenter randomized study comparing peginterferon α-2a plus adefovir vs. peginterferon α-2a plus placebo vs. adefovir in chronic delta hepatitis,” Journal of Hepatology, vol. 46, Supplement 1, p. S4, 2007.
[37]  C. Yurdaydin, H. Bozkaya, S. Gürel et al., “Famciclovir treatment of chronic delta hepatitis,” Journal of Hepatology, vol. 37, no. 2, pp. 266–271, 2002.
[38]  G. A. Niro, A. Ciancio, G. B. Gaeta et al., “Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta,” Hepatology, vol. 44, no. 3, pp. 713–720, 2006.
[39]  M. Rizzetto, F. Rosina, and G. Saracco, “Treatment of chronic delta hepatitis with α-2 recombinant interferon,” Journal of Hepatology, vol. 3, no. 2, pp. S229–S233, 1986.
[40]  P. Farci, L. Chessa, C. Balestrieri, G. Serra, and M. E. Lai, “Treatment of chronic hepatitis D,” Journal of Viral Hepatitis, vol. 14, no. 1, pp. 58–63, 2007.
[41]  C. Castelnau, F. Le Gal, M.-P. Ripault et al., “Efficacy of peginterferon alpha-2b in chronic hepatitis delta: relevance of quantitative RT-PCR for follow-up,” Hepatology, vol. 44, no. 3, pp. 728–735, 2006.
[42]  A. Erhardt, W. Gerlich, C. Starke et al., “Treatment of chronic hepatitis delta with pegylated interferon-α2b,” Liver International, vol. 26, no. 7, pp. 805–810, 2006.
[43]  B. B. Bordier, J. Ohkanda, P. Liu et al., “In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus,” Journal of Clinical Investigation, vol. 112, no. 3, pp. 407–414, 2003.
[44]  L.-F. He, E. Ford, P. H. Purcell, W. T. London, J. Phillips, and J. L. Gerin, “The size of the hepatitis delta agent,” Journal of Medical Virology, vol. 27, no. 1, pp. 31–33, 1989.
[45]  S. Gudima, J. Chang, G. Moraleda, A. Azvolinsky, and J. Taylor, “Parameters of human hepatitis delta virus genome replication: the quantity, quality, and intracellular distribution of viral proteins and RNA,” Journal of Virology, vol. 76, no. 8, pp. 3709–3719, 2002.
[46]  M. Engelke, K. Mills, S. Seitz et al., “Characterization of a hepatitis B and hepatitis delta virus receptor binding site,” Hepatology, vol. 43, no. 4, pp. 750–760, 2006.
[47]  D. Glebe and S. Urban, “Viral and cellular determinants involved in hepadnaviral entry,” World Journal of Gastroenterology, vol. 13, no. 1, pp. 22–38, 2007.
[48]  J. M. Taylor and Z. Han, “Purinergic receptor functionality is necessary for infection of human hepatocytes by hepatitis delta virus and hepatitis b virus,” PLoS ONE, vol. 5, no. 12, Article ID e15784, 2010.
[49]  O. L. Longarela, T. T. Schmidt, K. Sch?neweis, R. Romeo, H. Wedemeyer, et al., “Proteoglycans act as cellular hepatitis delta virus attachment receptors,” PLoS ONE, vol. 8, Article ID e58340, 2013.
[50]  H. Yan, G. Zhong, G. Xu, W. He, Z. Jing, et al., “Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus,” ELife, vol. 1, Article ID e00049, 2012.
[51]  P. Dény, “Hepatitis delta virus genetic variability: from genotypes I, II, III to eight major clades?” Current Topics in Microbiology and Immunology, vol. 307, pp. 151–171, 2006.
[52]  M. Y. P. Kuo, J. Goldberg, L. Coates, W. Mason, J. Gerin, and J. Taylor, “Molecular cloning of hepatitis delta virus RNA from an infected woodchuck liver: sequence, structure, and applications,” Journal of Virology, vol. 62, no. 6, pp. 1855–1861, 1988.
[53]  P.-J. Chen, G. Kalpana, and J. Goldberg, “Structure and replication of the genome of the hepatitis δ virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 22, pp. 8774–8778, 1986.
[54]  S.-Y. Hsieh and J. Taylor, “Regulation of polyadenylation of hepatitis delta virus antigenomic RNA,” Journal of Virology, vol. 65, no. 12, pp. 6438–6446, 1991.
[55]  S. Gudima, S.-Y. Wu, C.-M. Chiang, G. Moraleda, and J. Taylor, “Origin of hepatitis delta virus mRNA,” Journal of Virology, vol. 74, no. 16, pp. 7204–7210, 2000.
[56]  L. Sharmeen, M. Y. P. Kuo, G. Dinter-Gottlieb, and J. Taylor, “Antigenomic RNA of human hepatitis delta virus can undergo self-cleavage,” Journal of Virology, vol. 62, no. 8, pp. 2674–2679, 1988.
[57]  A. D. Branch, B. J. Benenfeld, B. M. Baroudy, F. V. Wells, J. L. Gerin, and H. D. Robertson, “An ultraviolet-sensitive RNA structural element in a viroid-like domain of the hepatitis delta virus,” Science, vol. 243, no. 4891, pp. 649–652, 1989.
[58]  M. D. Been, “HDV ribozymes,” Current Topics in Microbiology and Immunology, vol. 307, pp. 47–65, 2006.
[59]  A. R. Ferré-D'Amaré, K. Zhou, and J. A. Doudna, “Crystal structure of a hepatitis delta virus ribozyme,” Nature, vol. 395, no. 6702, pp. 567–574, 1998.
[60]  K. Salehi-Ashtiani, A. Lupták, A. Litovchick, and J. W. Szostak, “A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene,” Science, vol. 313, no. 5794, pp. 1788–1792, 2006.
[61]  C.-H. T. Webb, N. J. Riccitelli, D. J. Ruminski, and A. Lupták, “Widespread occurrence of self-cleaving ribozymes,” Science, vol. 326, no. 5955, p. 953, 2009.
[62]  J. M. Taylor, “Hepatitis delta virus: cis and trans functions required for replication,” Cell, vol. 61, no. 3, pp. 371–373, 1990.
[63]  C. E. Reid and D. W. Lazinski, “A host-specific function is required for ligation of a wide variety of ribozyme-processed RNAs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 1, pp. 424–429, 2000.
[64]  L. Sharmeen, M. Y.-P. Kuo, and J. Taylor, “Self-ligating RNA sequences on the antigenome of human hepatitis delta virus,” Journal of Virology, vol. 63, no. 3, pp. 1428–1430, 1989.
[65]  J. M. Taylor, “Chapter 3 replication of the hepatitis delta virus RNA genome,” Advances in Virus Research, vol. 74, pp. 103–121, 2009.
[66]  J. Chang, X. Nie, E. C. Ho, Z. Han, and J. Taylor, “Transcription of hepatitis delta virus RNA by RNA polymerase II,” Journal of Virology, vol. 82, no. 3, pp. 1118–1127, 2008.
[67]  V. S. Greco-Stewart, P. Miron, A. Abrahem, and M. Pelchat, “The human RNA polymerase II interacts with the terminal stem-loop regions of the hepatitis delta virus RNA genome,” Virology, vol. 357, no. 1, pp. 68–78, 2007.
[68]  J. Filipovska and M. M. Konarska, “Specific HDV RNA-templated transcription by pol II in vitro,” RNA, vol. 6, no. 1, pp. 41–54, 2000.
[69]  T. B. Macnaughton, S. T. Shi, L. E. Modahl, and M. M. C. Lai, “Rolling circle replication of hepatitis delta virus RNA is carried out by two different cellular RNA polymerases,” Journal of Virology, vol. 76, no. 8, pp. 3920–3927, 2002.
[70]  L. E. Modahl, T. B. Macnaughton, N. Zhu, D. L. Johnson, and M. M. C. Lai, “RNA-dependent replication and transcription of hepatitis delta virus RNA involve distinct cellular RNA polymerases,” Molecular and Cellular Biology, vol. 20, no. 16, pp. 6030–6039, 2000.
[71]  J. P. Tavanez, C. Cunha, M. C. A. Silva, E. David, J. Monjardino, and M. Carmo-Fonseca, “Hepatitis delta virus ribonucleoproteins shuttle between the nucleus and the cytoplasm,” RNA, vol. 8, no. 5, pp. 637–646, 2002.
[72]  V. S. Greco-Stewart, E. Schissel, and M. Pelchat, “The hepatitis delta virus RNA genome interacts with the human RNA polymerases I and III,” Virology, vol. 386, no. 1, pp. 12–15, 2009.
[73]  J. Chang and J. Taylor, “In vivo RNA-directed transcription, with template switching, by a mammalian RNA polymerase,” EMBO Journal, vol. 21, no. 1-2, pp. 157–164, 2002.
[74]  T.-B. Fu and J. Taylor, “The RNAs of hepatitis delta virus are copied by RNA polymerase II in nuclear homogenates,” Journal of Virology, vol. 67, no. 12, pp. 6965–6972, 1993.
[75]  J. Taylor, “Virology of hepatitis D virus,” Seminars in Liver Disease, vol. 32, pp. 195–200, 2012.
[76]  M. M. C. Lai, “RNA replication without RNA-dependent RNA polymerase: surprises from hepatitis delta virus,” Journal of Virology, vol. 79, no. 13, pp. 7951–7958, 2005.
[77]  A. G. Polson, B. L. Bass, and J. L. Casey, “Erratum: RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase,” Nature, vol. 381, no. 6580, p. 346, 1996.
[78]  J. L. Casey, “Hepatitis delta virus RNA editing,” in Hepatitis Delta Virus, H. Handa and Y. Yamaguchi, Eds., pp. 52–65, Georgetown Landes Bioscience, Austin, Tex, USA, 2006.
[79]  C. Alves, N. Freitas, and C. Cunha, “Characterization of the nuclear localization signal of the hepatitis delta virus antigen,” Virology, vol. 370, no. 1, pp. 12–21, 2008.
[80]  C.-Z. Lee, J.-H. Lin, M. Chao, K. McKnight, and M. M. C. Lai, “RNA-binding activity of hepatitis delta antigen involves two arginine- rich motifs and is required for hepatitis delta virus RNA replication,” Journal of Virology, vol. 67, no. 4, pp. 2221–2227, 1993.
[81]  C.-H. Lee, S. C. Chang, C. H. H. Wu, and M.-F. Chang, “A novel chromosome region maintenance 1-independent nuclear export signal of the large form of hepatitis delta antigen that is required for the viral assembly,” The Journal of Biological Chemistry, vol. 276, no. 11, pp. 8142–8148, 2001.
[82]  J. S. Glenn, J. A. Watson, C. M. Havel, and J. M. White, “Identification of a prenylation site in delta virus large antigen,” Science, vol. 256, no. 5061, pp. 1331–1333, 1992.
[83]  J. C. Otto and P. J. Casey, “The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells,” The Journal of Biological Chemistry, vol. 271, no. 9, pp. 4569–4572, 1996.
[84]  S. B. Hwang and M. M. C. Lai, “Isoprenylation masks a conformational epitope and enhances trans-dominant inhibitory function of the large hepatitis delta antigen,” Journal of Virology, vol. 68, no. 5, pp. 2958–2964, 1994.
[85]  C.-Z. Lee, P.-J. Chen, M. M. C. Lai, and D.-S. Chen, “Isoprenylation of large hepatitis delta antigen is necessary but not sufficient for hepatitis delta virus assembly,” Virology, vol. 199, no. 1, pp. 169–175, 1994.
[86]  J.-J. Mu, H.-L. Wu, B.-L. Chiang, R.-P. Chang, D.-S. Chen, and P.-J. Chen, “Characterization of the phosphorylated forms and the phosphorylated residues of hepatitis delta virus delta antigens,” Journal of Virology, vol. 73, no. 12, pp. 10540–10545, 1999.
[87]  T.-S. Yeh, S. J. Lo, P.-J. Chen, and Y.-H. W. Lee, “Casein kinase II and protein kinase C modulate hepatitis delta virus RNA replication but not empty viral particle assembly,” Journal of Virology, vol. 70, no. 9, pp. 6190–6198, 1996.
[88]  C.-W. Chen, Y.-G. Tsay, H.-L. Wu, C.-H. Lee, D.-S. Chen, and P.-J. Chen, “The double-stranded RNA-activated kinase, PKR, can phosphorylate hepatitis D virus small delta antigen at functional serine and threonine residues,” The Journal of Biological Chemistry, vol. 277, no. 36, pp. 33058–33067, 2002.
[89]  Y.-S. Chen, W.-H. Huang, S.-Y. Hong, Y.-G. Tsay, and P.-J. Chen, “ERK1/2-mediated phosphorylation of small hepatitis delta antigen at serine 177 enhances hepatitis delta virus antigenomic RNA replication,” Journal of Virology, vol. 82, no. 19, pp. 9345–9358, 2008.
[90]  S.-Y. Hong and P.-J. Chen, “Phosphorylation of serine 177 of the small hepatitis delta antigen regulates viral antigenomic RNA replication by interacting with the processive RNA polymerase II,” Journal of Virology, vol. 84, no. 6, pp. 1430–1438, 2010.
[91]  W.-H. Huang, R.-T. Mai, and Y.-H. W. Lee, “Transcription factor YY1 and its associated acetyltransferases CBP and p300 interact with hepatitis delta antigens and modulate hepatitis delta virus RNA replication,” Journal of Virology, vol. 82, no. 15, pp. 7313–7324, 2008.
[92]  J.-J. Mu, Y.-G. Tsay, L.-J. Juan et al., “The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis,” Virology, vol. 319, no. 1, pp. 60–70, 2004.
[93]  C.-H. Tseng, K.-S. Jeng, and M. M. C. Lai, “Transcription of subgenomic mRNA of hepatitis delta virus requires a modified hepatitis delta antigen that is distinct from antigenomic RNA synthesis,” Journal of Virology, vol. 82, no. 19, pp. 9409–9416, 2008.
[94]  Y.-J. Li, M. R. Stallcup, and M. M. C. Lai, “Hepatitis delta virus antigen is methylated at arginine residues, and methylation regulates subcellular localization and RNA replication,” Journal of Virology, vol. 78, no. 23, pp. 13325–13334, 2004.
[95]  C.-H. Tseng, T.-S. Cheng, C.-Y. Shu, K.-S. Jeng, and M. M. C. Lai, “Modification of small hepatitis delta virus antigen by SUMO protein,” Journal of Virology, vol. 84, no. 2, pp. 918–927, 2010.
[96]  M. Chao, S.-Y. Hsieh, and J. Taylor, “Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limiting genome replication,” Journal of Virology, vol. 64, no. 10, pp. 5066–5069, 1990.
[97]  V. Williams, S. Brichler, N. Radjef et al., “Hepatitis delta virus proteins repress hepatitis B virus enhancers and activate the alpha/beta interferon-inducible MxA gene,” Journal of General Virology, vol. 90, no. 11, pp. 2759–2767, 2009.
[98]  S. K. Wong and D. W. Lazinski, “Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 23, pp. 15118–15123, 2002.
[99]  H.-C. Chou, T.-Y. Hsieh, G.-T. Sheu, and M. M. C. Lai, “Hepatitis delta antigen mediates the nuclear import of hepatitis delta virus RNA,” Journal of Virology, vol. 72, no. 5, pp. 3684–3690, 1998.
[100]  A. G. Polson, H. L. Ley III, B. L. Bass, and J. L. Casey, “Hepatitis delta virus RNA editing is highly specific for the amber/W site and is suppressed by hepatitis delta antigen,” Molecular and Cellular Biology, vol. 18, no. 4, pp. 1919–1926, 1998.
[101]  G. C. Jayan and J. L. Casey, “Increased RNA editing and inhibition of hepatitis delta virus replication by high-level expression of ADAR1 and ADAR2,” Journal of Virology, vol. 76, no. 8, pp. 3819–3827, 2002.
[102]  Y. Yamaguchi, J. Filipovska, K. Yano et al., “Stimulation of RNA polymerase II elongation by hepatitis delta antigen,” Science, vol. 293, no. 5527, pp. 124–127, 2001.
[103]  Y. Yamaguchi, T. Mura, S. Chanarat, S. Okamoto, and H. Handa, “Hepatitis delta antigen binds to the clamp of RNA polymerase II and affects transcriptional fidelity,” Genes to Cells, vol. 12, no. 7, pp. 863–875, 2007.
[104]  D. W. Lazinski and J. M. Taylor, “Expression of hepatitis delta virus RNA deletions: cis And trans requirements for self-cleavage, ligation, and RNA packaging,” Journal of Virology, vol. 68, no. 5, pp. 2879–2888, 1994.
[105]  C.-C. Wang, T.-C. Chang, C.-W. Lin et al., “Nucleic acid binding properties of the nucleic acid chaperone domain of hepatitis delta antigen,” Nucleic Acids Research, vol. 31, no. 22, pp. 6481–6492, 2003.
[106]  C. Dan, D. Haussecker, H. Yong, and M. A. Kay, “Combined proteomic-RNAi screen for host factors involved in human hepatitis delta virus replication,” RNA, vol. 15, no. 11, pp. 1971–1979, 2009.
[107]  A. Casaca, M. Fardilha, E. Da Cruz E Silva, and C. Cunha, “The heterogeneous ribonuclear protein C interacts with the hepatitis delta virus small antigen,” Virology Journal, vol. 8, article 358, 2011.
[108]  C. Alves, H. Cheng, H. Roder, and J. Taylor, “Intrinsic disorder and oligomerization of the hepatitis delta virus antigen,” Virology, vol. 407, no. 2, pp. 333–340, 2010.

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