Summary
Hepatitis delta virus (HDV) is a defective virus dependent on hepatitis B virus (HBV) for infection. Superinfection by HDV on a HBV chronic carrier state is generally associated with an exacerbation of the underlying liver disease. Several HDV RNA sequences are now available from different viral strains which show a relatively high conservation of sequences, although some differences are shown in some parts of the viral genome. The delta antigen (HDAg) is the only identified viral protein. The diagnosis of delta hepatitis is generally based on the detection of anti-HD antibodies (total and IgM) in serum and detection of HDAg in the liver; this antigen is detectable in serum only for a short time at the onset of acute infection. The use of molecular hybridization techniques for HDV RNA identification has recently proved to be a powerful tool in the appraisal of HDV infections, mainly in patients with acute hepatitis and in immunocompromised subjects, where the pattern of serological HDV markers may be modified. Among these techniques, the polymerase chain reaction (PCR) appears to be very sensitive in detecting HDV RNA sequences, both in liver and in serum samples. This approach is most useful when only small amounts of serum HDV RNA are present, for example in the later stages of chronic infection, in IFN-treated patients, or in otherwise inadequately preserved sera. PCR is also useful in interpreting doubtful Slot test results which could correspond either to a negative or to a weak positive. In addition, HDV PCR is a means for cloning and sequencing and for analyzing HDV genetic variability. We analyzed, in a relatively short time, the whole genome of HDV from the liver of an infected woodchuk after several passages, then compared selected parts of the HDV genome with two unrelated HDV strains isolated from humans. PCR allowed, in these circumstances, a better appraisal in the implications of HDV genome variability.
Anna Linda Zignego was supported by the Natlonal Research Council, targeted project “Prevention and Control Disease Factors”, subproject “SP3”, contract no. 91.00168
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References
Bonino F, Hoyer B, Ford E, Shih JW, Purcell RH, Gerin JL (1981) The delta agent: HBsAg particles with delta antigen and RNA in the serum of HBV carrier. Hepatology 1:127–131
Chang MF, Baker SC, Soe LH, Kamahora T, Makino S, Govindarajan S, Lai MMC (1988) Human hepatitis delta antigen is a nuclear phosphoprotein with RNA-binding activity. J Virol 62:2403–2410
Chao M, Hsieh S Y, Taylor J (1990) Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self limiting genome replication. J Virol 64:5066–5069
Chen PJ, Kalpana G, Goldberg J, Mason W, Werner B, Gerin J, Taylor J (1986) Structure and replication of the genome of the hepatitis delta virus. Proc Natl Acad Sci USA 83:8774–8778
Cole SM, Gowans EJ, Macnaughton TB, De La M, Hall P, Burrell CJ (1991) Direct evidence for cytotoxicity associated with expression of hepatitis delta virus antigen. Hepatology 13:645–851
Dennistom KJ, Hoyer BH, Smedile A, Wells FV, Nelson J, Gerin JL (1986) Cloned fragment of the hepatitis delta virus RNA genome: sequence and diagnostic applications. Science 232:873–875
Farza H, Salmon AM, Hadchouel M, Moreau JL, Babinet C, Tiollais P, Porcell C (1987) Hepatitis B surface antigen gene expression is regulated by sex steroids and glucocorticoids in transgenic mice. Proc Natl Acad Sci USA 84:1187–1191
Gerken G, Paterlini P, Manns M, Housset C, Terre S, Dienes HP, Hess G, Gerlich WH, Berthelot P, Meyerzum Buschenfelde KH, Brechot C (1990) Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship to Pre-S and S-encoded viral surface antigens. Hepatology 13:158–166
Glenn J, Taylor J, White J (1990) In vitro-synthesized delta virus RNA initiates genome replication in cultured cells. J Virol 164:3104–3107
Kos A, Dijkema R, Arnberg AC, Wan der Meide PH, Schellekens H (1986) The hepatitis delta virus possesses a circular RNA. Nature 323:558–560
Kuo M, Goldberg J, Coates L, Mason W, Gerin J, Taylor J (1988) Molecular cloning of hepatitis delta virus RNA from an infected woodchuck liver: sequence, structure and applications. J Virol 62:1855–1861
Kuo MY-P, Chao M, Taylor J (1989) Initiation of replication of human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol 63:1945–1950
Macnaughton TB, Gowans EJ, Reinboth B, Jilbert AR, Burrel CJ (1990) Stable expression of hepatitis delta virus antigen in a eukaryotic cell line. J Gen Virol 71:1339–1345
Makino S, Chang MF, Shieh CK, Kamahora T, Vannier DM, Govindarajan S, Lai MM (1987) Molecular cloning and sequencing of a human hepatitis delta virus RNA. Nature 329:343–346
Negro F, Korba BE, Forzani B, Barondy BM, Brown TL, Gerin JL, Ponzetto A (1989) Hepatitis delta virus (HDV) and woodchuck hepatitis virus (WHV) nucleic acids in tissues of HDV-infected chronic WHV carrier woodchuck. J Virol 63:1612–1618
Ponzetto A, Cote PJ, Popper H, Hoyer BH, London WT, Ford EL, Bonino F, Purcell RH, Gerin JL (1984) Transmission of the hepatitis B virus-associated delta agent to the eastern woodchuck. Proc Natl Acad Sci USA 81:2208–2212
Ponzetto A, Forzani B, Smedile A, Hele C, Avanzini L, Novara R, Canese M (1987) Acute and chronic delta infection in the woodchuck. Progr Clin Biol Res 234:37–46
Popper H, Thung SN, Gerber MA, Hadler SC, De Monzon M, Ponzetto A, Anzola E, Rivera D, Mondolsi A, Bracho A, Francis DP, Gerin JL, Maynard JE, Purcell RH (1983) Histologie studies of severe delta agent infection in Venezuelan Indians. Hepatology 3:906–912
Rasshofer R, Buti M, Esteban R, Jardi R, Roggerdorf M (1987) Demonstration of hepatitis D virus RNA in patients with chronic active hepatitis. J Infect Dis 157:191–195
Reynes M, Zignego AL, Samuel D, Fabiani B, Gugenheim J, Tricottet V, Brechot C, Bismuth H (1989) Graft hepatitis delta virus reinfection after orthotopic liver transplantation in HDV cirrhosis. Transplant Proc 21:2424–2425
Rizzetto M (1983) The delta agent. Hepatology 3:729–737
Rizzetto M, Canese MG, Arico S, Crivelli O, Bonino F, Trepo CG, Verme G (1977) Immunofluorescence detection of a new antigen antibody system (delta/anti-delta) associated to the hepatitis B virus in the liver and in the serum of HBsAg carriers. GUT 18:997–1003
Rizzetto M, Canese M, Gerin JL, London WT, Sly DL, Purcell RH (1980 a) Transmission of the hepatitis B virus associated delta antigen to chimpanzees. J Infect Dis 141:590–602
Rizzetto M, Hoyer B, Canese M, Shih JW-K, Purcell RH, Gerin J (1980 b) Delta agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infect chimpanzees. Proc Natl Acad Sci USA 77:6124–6128
Saiki RK (1989) The design and optimization of the PCR. In: Erlich HA (ed) PCR technology: principles and applications for DNA amplification. Stockton, New York, pp 7–16
Saldanha J, di Blasi F, Blas C, Velosa J, Ramalho RM, di Marco V, Mora L, de Moura MC, Carreno V, Craxi A (1989) Detection of hepatitis delta virus RNA in chronic liver disease. Hepatology 9:23–28
Saldanha JA, Thomas HC, Monjardino JP (1990) Cloning and sequencing of RNA of hepatitis delta virus isolated from human serum. J Gen Virol 71:1603–1606
Sharmeen L, Kuo M, Dinter-Gottelieb G, Taylor J (1988) Antigenomic RNA of hepatitis delta virus can undergo self cleavage. J Virol 62:2674–2679
Smedile A, Rizzetto M, Denninston K, Bonino F, Wells F, Verme G, Consolo F, Hoyer B, Purcell RH, Gerin JL (1986) Type D hepatitis: the clinical significance of hepatitis D virus RNA in serum as detected by a hybridization-based assay. Hepatology 6:1297–1302
Taylor J, Mason W, Summers J, Goldberg J, Aldrich C, Coates L, Gerin J, Gowans E (1987) Replication of human hepatitis delta virus in primary cultures of woodchuck hepatocytes. J Virol 61:2891–2895
Verme G, Rocca G, Rizzi R, Mollo F, David E, Solcia E, Sessa F (1990) Histopathology of chronic delta hepatitis. In: Verma G, Bonino F, Rizzetto M (eds) Viral hepatitis and delta infection. Liss, New York, pp 169–176
Wang K-S, Choo Q-L, Weiner AJ, Ou J-H, Najarian RC, Thayer RM, Mullenbach GT, Denniston KJ, Gerin JL, Hougton M (1986) Structure, sequence and expression of the hepatitis delta viral genome. Nature 323:508–514, 328:456
Zignego AL, Deny P, Feray C, Ponzetto A, Gentilini P, Tiollais P, Brechot C (1990 a) Amplification of hepatitis delta virus RNA sequences by polymerase chain reaction: a tool for viral detection and cloning. Mol Cell Probes 4:43–51
Zignego AL, Dubois F, Samuel D, Reynes M, Gentilini P, Bysmuth A, Gaudeau A, Benhamou JP, Tiollais P, Bismuth H, Brechot C (1990 b) Serum hepatitis delta RNA in patients with delta hepatitis and in liver graft recipients. J Hepatol 11:102–110
Zignego AL, Samuel D, Dubois F, Reynes M, Gentilini P, Gaudeau A, Benhamou JP, Tiollais P, Bismuth H, Brechot C (1990c) Liver transplant recipients as a model for the study of HDV infection natural history. In: Dianzani MU, Gentilini P (eds) Chronic liver damage. Excerpta Medica, Amsterdam, pp 137–144
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Zignego, A.L., Deny, P., Gentilini, P., Brechot, C. (1992). Polymerase Chain Reaction for Hepatitis Delta Virus RNA Identification and Characterization. In: Becker, Y., Darai, G. (eds) Diagnosis of Human Viruses by Polymerase Chain Reaction Technology. Frontiers of Virology, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84766-0_9
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