Skip to main content
SpringerLink
Log in

Viral DNA Synthesis

  • Chapter
Hepadnaviruses

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 168))

Abstract

In 1973, it was first discovered that human hepatitis B virus (HBV) preparations from sera of chronically infected individuals contain an endogenous polymerase activity capable of carrying out a repair reaction on the viral DNA template in the presence of magnesium and nucleotide triphosphates (Kaplan et al. 1973). The polymerase was shown to be resistant to solubilization by nonionic detergents, a condition precluding the characterization of enzymatic activities with exogenous RNA or DNA templates. With the help of electron microscopic characterization of the predominant species in virus preparations (Robinson et al. 1974), together with sedimentation and electrophoretic analysis of the DNA products of the endogenous polymerase reaction (Kaplan et al. 1973; Summers et al. 1975), the structure of the viral genome was identified. HBV has a ca. 3 kbp-long genome held in a relaxed circular conformation by a short, cohesive overlap (ca. 0.2 kbp) between the 5′ ends of the two DNA strands (Summers et al. 1975; Sattler and Robinson 1979; Ganem et al. 1982; Molnar-Kimber et al. 1984). One strand, subseqently shown to encode the viral proteins and hence termed minusstrand DNA (Pasek et al. 1979), is complete whereas the other strand, plus-strand DNA, is incomplete and heterogeneous in length (Summers et al. 1975). Thus, the repair reaction carried out by the endogenous polymerase in vitro fills in the single-stranded gap, which can span up to 50% of the viral genome. These characteristics of the HBV genome have served, along with other criteria, to identify additional members of the hepadnaviral family, including woodchuck hepatitis virus (WHV) (Summers et al. 1978), ground squirrel hepatitis virus (GSHV) (Marion et al. 1980), duck hepatitis B virus (DHBV) (Mason et al. 1980), and heron hepatitis B virus (HHBV) (Sprengel et al. 1988).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Acs G, Sells MA, Purcell RH, Price P, Engle R, Shapiro M, Popper H (1987) Hepatitis B virus produced by transfected Hep G2 cells causes hepatitis in chimpanzees. Proc Natl Acad Sci USA 84: 4641–4644

    Article  PubMed  CAS  Google Scholar 

  • Aldrich CE, Coates L, Wu T-T, Newbold J, Tennant BC, Summers J, Seeger C, Mason WS (1989) In vitro infection of woodchuck hepatocytes with woodchuck hepatitis virus and ground squirrel hepatitis virus. Virology 172: 247–252

    Article  PubMed  CAS  Google Scholar 

  • Bartenschlager R, Schaller H (1988) The amino-terminal domain of the hepadnaviral P-gene encodes the terminal protein (genome-linked protein) believed to prime reverse transcription. EMBO J 7:4185–4192

    PubMed  CAS  Google Scholar 

  • Brown DR, Roth MJ, Reinberg D, Hurwitz J (1984) Analysis of bacteriphage phjX174 gene A proteinmediated termination and reinitiation of phiX DNA synthesis. J Biol Chem 259: 10545–10555

    PubMed  CAS  Google Scholar 

  • Büscher M, Reiser W, Will H, Schaller H (1985) Transcripts and the putative RNA pregenome of duck hepatitis B virus implications for reverse transcription. Cell 40: 717–724

    Article  PubMed  Google Scholar 

  • Chang CM, Jeng KS, Hu CP, Lo SJ, Su TS, Ting LP, Chou CK, Ha SH, Pfaff E, Salfeld J (1987) Production of hepatitis B virus in vitro by transient expression of cloned HBV DNA in a hepatoma cell line. EMBO J 6: 675–680

    PubMed  CAS  Google Scholar 

  • Chang L-J, Pryciak P, Ganem D, Varmus HE (1989) Biosynthesis of the reverse transcriptase of hepatitis B viruses involves de novo translation initiation not ribosomal frameshifting. Nature 337: 364–368

    Article  PubMed  CAS  Google Scholar 

  • Covey SN, Turner D, Mulder G (1983) A small DNA molecule containing covalently-linked ribonucleotides originates from the large intergenic region of the cauliflower mosaic virus genome. Nucleic Acids Res 11: 251–264

    Article  PubMed  CAS  Google Scholar 

  • Enders GH, Ganem D, Varmus HE (1985) Mapping the major transcripts of ground squirrel hepatitis virus: The presumptive template for reverse transcriptase is terminally redundant. Cell 42 : 297–308

    Article  PubMed  CAS  Google Scholar 

  • Enders GH, Ganem D, Varmus HE (1987) 5′-Terminal sequences influence the segregation of ground squirrel hepatitis virus RNA into polyribosomes and viral core particles. J Virol 61: 35–41

    PubMed  CAS  Google Scholar 

  • Ganem D, Greenbaum L, Varmus HE (1982) Virion DNA of ground squirrel hepatitis virus structural charactrization and molecular cloning. J Virol 44: 374–383

    PubMed  CAS  Google Scholar 

  • Gerlich WH, Robinson WS (1980) Hepatitis B virus contains protein attached to the 5′ terminus of its complete DNA strand. Cell 21: 801–809

    Article  PubMed  CAS  Google Scholar 

  • Gripon P, Diot C, Theze N, Fourel I, Loreal O, Brechot C, Guguen-Guillouzo C (1988) Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide. J virol 62:4136–4143

    PubMed  CAS  Google Scholar 

  • Gumport RI, Lehman IR (1971) Structure of the DNA ligase-adenylate intermediate Lysine (e-amino)-linked adenosine monophosphoramidate. Proc Natl Acad Sci USA 68: 2559–2563

    Article  PubMed  CAS  Google Scholar 

  • Hirsch R, Colgrove R, Ganem D (1988) Replication of duck hepatitis B virus in two differentiated human hepatoma cell lines after transfection with cloned viral DNA. Virology 167: 136–142

    Article  PubMed  CAS  Google Scholar 

  • Junker M, Galle P, Schaller H (1987) Expression and replication of the hepatitis B virus genome under foreign promoter control. Nucleic Acids Res 15: 10117–10132

    Article  PubMed  CAS  Google Scholar 

  • Kaplan PM, Greenman RL, Gerin JL, Purcell RH, Robinson WS (1973) DNA polymerase associated with human hepatitis B antigen. J Virol 12: 995–1005

    PubMed  CAS  Google Scholar 

  • Kotewicz ML, D’Alessio JM, Driftmier KM, Blodgett KP, Gerard GF (1985) Cloning and overexpression of Moloney murine leukemia virus reverse transcriptase in Escherichia coli. Gene 35: 249–258

    Article  PubMed  CAS  Google Scholar 

  • Lavine J, Hirsch R, Ganem D (1989) A system for studying the selective encapsidation of hepadnavirus RNA. J Virol 63: 4257–4263

    PubMed  CAS  Google Scholar 

  • Lien J, Aldrich CE, Mason WS (1986) Evidence that a capped oligoribonucleotide is the primer for duck hepatitis B virus plus strand DNA synthesis. J Virol 57: 229–236

    PubMed  CAS  Google Scholar 

  • Lien J, Petcu DJ, Aldrich CE, Mason WS (1987) Initiation and termination of duck hepatitis B virus DNA synthesis during virus maturation. J Virol 61: 3832–3840

    PubMed  CAS  Google Scholar 

  • Marion PL, Oshiro LS, Regnery DC, Scullard GH, Robinson WS (1980) A virus in Beechey ground squirrels that is related to hepatitis B virus of humans. Proc Natl Acad Sci USA 77: 2941–2945

    Article  PubMed  CAS  Google Scholar 

  • Mason WS, Seal G, Summers J (1980) Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus. J Virol 36: 829–836

    PubMed  CAS  Google Scholar 

  • Mason WS, Aldrich C, Summers J, Taylor JM (1982) Asymmetric replication of duck hepatitis B virus DNA in liver cells: Free minus-strand DNA. Proc Natl Acad Sci USA 79: 3997–4001

    Article  PubMed  CAS  Google Scholar 

  • Mason WS, Halpern MS, England JM, Seal G, Egan J, Coates L, Aldrich C, Summers J (1983) Experimental transmission of duck hepatitis B virus. Virology 131: 375–384

    Article  PubMed  CAS  Google Scholar 

  • Mason WS, Lien J, Petcu DJ, Coates L, London WT, O’Connell A, Aldrich C, Custer PR (1987a) In vivo and in vitro studies on duck hepatitis B virus. Replication. In: Robinson WS, Kolke K, Will H (eds) Hepadna viruses. Liss, New York, pp 3–16

    Google Scholar 

  • Mason WS, Taylor JM, Hull R (1978b) Retroid virus genome replication. Adv virus Res 32: 35–96

    Article  Google Scholar 

  • Miller RH, Robinson WS (1984) Hepatitis B virus DNA in nuclear and cytoplasmic fractions of infected human liver. Virology 137: 390–399

    Article  PubMed  CAS  Google Scholar 

  • Molnar-Kimber KL, Summers JW, Taylor JM, Mason WS (1983) Protein covalently bound to minus strand DNA intermediates of duck hepatitis B virus. J Virol 45: 165–172

    PubMed  CAS  Google Scholar 

  • Molnar-Kimber KL, Summers JW, Mason WS (1984) Mapping of the cohesive overlap of duck hepatitis B virus DNA and of the site of initiation of reverse transcription. J Virol 51: 181–191

    PubMed  CAS  Google Scholar 

  • Moroy T, Etiemble J, Trepo C, Tiollais P, Buendia MA (1985) Transcription of woodchuck hepatitis virus in the chronically infected liver. EMBO J 4: 1507–1514

    PubMed  CAS  Google Scholar 

  • Niepmann-Junker M, Bartenschlager R, Schaller H (1990) A short cis-acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA. EMBO 9: 3389–3396

    Google Scholar 

  • Ochiya T, Tsurimoto T, Ueda K, Okubo K, Shiozawa M, Matsubara K (1989) An in vitro system for infection with hepatitis B virus that uses primary human fetal hepatocytes. Proc Natl Acad Sci USA 86: 1875–1879

    Article  PubMed  CAS  Google Scholar 

  • Pasek M, Goto T, Gilbert W, Zink B, Schaller H, MacKay P, Leadbetter G, Murray K (1979) Hepatitis B virus genes and their expression in E coli. Nature 282: 575–579

    Article  PubMed  CAS  Google Scholar 

  • Petcu DJ, Aldrich CE, Coates L, Taylor JM, Mason WS (1988) Suramin inhibits in vitro infection by duck hepatitis B virus, Rous sarcoma virus, and hepatitis delta virus. J Virol 167: 385–392

    CAS  Google Scholar 

  • Pugh JC, Yaginuma K, Koike K, Summers J (1988) Duck hepatitis B virus (DHBV) particles produced by transient expression of DHBV DNA in a human hepatoma cell line are infectious in vitro. J Virol 62:3513–3616

    PubMed  CAS  Google Scholar 

  • Pugh JC, Summers J (1989) Infection and uptake of duck hepatitis B virus by duck hepatocytes maintained in the presence of dimethyl sulfate. J Virol 172: 564–572

    Article  CAS  Google Scholar 

  • Radziwill G, Zentgraf H, Schaller H, Bosch V (1988) The duck hepatitis B virus polymerase is tightly associated with the viral core structure and unable to switch to an exogenous template. Virology 163: 123–132

    Article  PubMed  CAS  Google Scholar 

  • Radziwill G, Tucker W, Schaller H (1990) Mutational analysis of the hepatitis B virus P gene product domain structure and RNAseH activity. J Virol 64: 613–620

    PubMed  CAS  Google Scholar 

  • Rijnitjes PJM, Morshage HJ, Yap SH (1988) In vitro infection of primary cultures of cryopreserved adult human hepatocytes with hepatitis B virus. Virus Res 10: 95–110

    Article  Google Scholar 

  • Robinson WS, Clayton DA, Greenman RL (1974) DNA of a human hepatitis B virus candidate. J Virol 14: 384–391

    PubMed  CAS  Google Scholar 

  • Roth MJ, Brown DR, Hurwitz J (1984) Analysis of bacteriophage phiX174 gene A protein-mediated termination and reinitiaion of phiX DNA synthesis. J Biol Chem 259: 10556–10568

    PubMed  CAS  Google Scholar 

  • Rothberg PG, Harris TJ, Nomoto A, Wimmer E (1978) The genome-linked protein of picornaviruses, V. O4-(5′-uridylyl) tyrosine is the bond between the genome-linked protein and the RNA of poliovirus. Proc Natl Acad Sci USA 75: 4868–4872

    Article  PubMed  CAS  Google Scholar 

  • Roychoudhury S, Shih C (1990) cis Rescue of a mutated reverse transcriptase of human hepatitis B virus by creation of an internal AUG. J Virol 64:1063–1069

    PubMed  CAS  Google Scholar 

  • Ruiz-Opazo N, Chakraborty PR, Shafritz DA (1982) Evidence for supercoiled hepatitis B virus DNA in chimpanzee liver and serum Dane particles: possible implications in persistent HBV infection. Cell 29: 129–138

    Article  PubMed  CAS  Google Scholar 

  • Salas M (1983) A new mechanism for the initiation of replication of φ29 and adenovirus DNA: priming by the terminal protein. In: Doerfler W (ed) The molecular biology of adenoviruses 1. 30 years of adenovirus research 1953–1983. Springer, Berlin Heidelberg New York, pp 89–106 (Current topics in microbiology and immunology, vol 109)

    Chapter  Google Scholar 

  • Sattler F, Robinson WS (1979) Hepatitis B viral DNA molecules have cohesive ends. J Virol 32: 226–233

    PubMed  CAS  Google Scholar 

  • Schlicht HJ, Radziwill G, Schaller H (1989) Synthesis and encapsidation of duck hepatitis B virus reverse transcriptase do not require formation of core-polymerase fusion proteins. Cell 56: 85–92

    Article  PubMed  CAS  Google Scholar 

  • Seeger C, Maragos J (1989) Molecular analysis of the function of direct repeats and a polypurine tract for plus-strand DNA priming in woodchuck hepatitis virus. J Virol 63: 1907–1915

    PubMed  CAS  Google Scholar 

  • Seeger C, Maragos J (1990) Identification and characterization of the woodchuck hepatitis virus origin of DNA replication. J Virol 64: 16–23

    PubMed  CAS  Google Scholar 

  • Seeger C, Ganem D, Varmus HE (1984) The cloned genome of ground squirrel hepatitis virus is infectious in the animal. Proc Natl Acad Sci USA 81: 5849–5852

    Article  PubMed  CAS  Google Scholar 

  • Seeger C, Ganem D, Varmus HE (1986) Biochemical and genetic evidence for the hepatitis B virus replication strategy. Science 232: 477–484

    Article  PubMed  CAS  Google Scholar 

  • Seeger C, Baldwin B, Tennant BC (1989) Expression of infectious woodchukc hepatitis virus in murine and avian fibroblasts. J Virol 63: 4665–4669

    PubMed  CAS  Google Scholar 

  • Sells MA, Chen M, Acs G (1987) Production of hepatitis B virus particles in hepG2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci USA 84: 1005–1009

    Article  PubMed  CAS  Google Scholar 

  • Sells MA, Zelent AZ, Shvartsman M, Acs G (1988) Replicative intermediates of hepatitis B virus in HepG2 cells that produce infectious virions. J Virol 62: 2836–2844

    PubMed  CAS  Google Scholar 

  • Shabarova ZA (1970) Synthetic nucleotide-peptides. In: Davidson JN, Cohn W (eds) Progress in nucleic acid research and molecular biology, vol. X. Academic, New York, pp 145–182

    Google Scholar 

  • Shih C, Li L-S, Roychoudhury S, Ho M-H (1989) In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. Proc Natl Acad Sci USA 86: 6323–6327

    Article  PubMed  CAS  Google Scholar 

  • Sprengel R, Kuhn C, Manso K, Will H (1984) Cloned duck hepatitis B virus DNA is infectious in pekin ducks. J Virol 52: 932–937

    PubMed  CAS  Google Scholar 

  • Sprengel R, Kaleta EF, Will H (1988) Isolation and characterization of a hepatitis B virus endemic in herons. J Virol 62: 3832–3839

    PubMed  CAS  Google Scholar 

  • Stillmann B (1989) Initiation of eukaryotic DNA replication in vitro. Annu Rev Cell Biol 5: 197–246

    Article  Google Scholar 

  • Summers J, Mason WS (1982) Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 29: 403–415

    Article  PubMed  CAS  Google Scholar 

  • Summers J, O’Connell A, Millman I (1975) Genome of hepatitis B virus restriction enzyme cleavage and structure of DNA extracted from Dane particles. Proc Natl Acad Sci USA 72: 4597–4601

    Article  PubMed  CAS  Google Scholar 

  • Summers J, Smolec JM, Snyder R (1978) A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci USA 75: 4533–4537

    Article  PubMed  CAS  Google Scholar 

  • Summers J, Smith PM, Horwich AL (1990) Hepadnaviral envelope proteins regulate covalently closed circular DNA amplification. J Virol 64: 2819–2824

    PubMed  CAS  Google Scholar 

  • Sureau C, Romet-Lemonne J, Mullins JI, Essex M (1987) Production of hepatitis B virus by a differentiated human hepatoma cell line after transfection with cloned circular HBV DNA. Cell 47:37–47

    Article  Google Scholar 

  • Sureau C, Eichberg JW, Hubbard GB, Romet-Lemonne JL, Essex M (1988) A molecularly cloned hepatitis B virus produced in vitro is infectious in a chimpanzee. J Virol 62: 3064–3067

    PubMed  CAS  Google Scholar 

  • Tagawa M, Omata M, Okuda K (1986) Appearance of viral RNA transcripts in the early stage of duck hepatitis B virus infection. Virology 152: 477–482

    Article  PubMed  CAS  Google Scholar 

  • Takeda N, Kuhn RJ, Yang O, Takegami T, Wimmer E (1986) Initiation of poliovirus plus-strand RNA synthesis in a membrane complex of infected HeLa cells. J Virol 60: 43–53

    PubMed  CAS  Google Scholar 

  • Tanese N, Roth M, Goff SP (1985) Expression of enzymatically active reverse transcriptase in Echerichia coli. Proc Natl Acad Sci USA 82: 4944–4948

    Article  PubMed  CAS  Google Scholar 

  • Tanese N, Sodrowski J, Haseltine WA, Goff SP (1986) Expression of reverse transcriptase activity of human T-lymphotropic virus type III (HTLV-III/LAV) in Escherichia coli. J Virol 59: 743–745

    PubMed  CAS  Google Scholar 

  • Taylor JM, Illmensee R (1975) Site on the RNA of an avian sarcoma virus at which primer is bound J Virol 16: 533–558

    Google Scholar 

  • Theze N, Gripon P, Fourel I, Hantz O, Trepo C, Guguen-Guillouzo C (1987) Maintenance of woodchuck hepatitis virus activity in primary cultures of woodchuck hepatocytes J Gen Virol 68: 1029–1039

    Article  PubMed  Google Scholar 

  • Tobin GJ, Young DC, Flanegan JB (1989) Self-catalyzed linkage of poliovirus terminal protein VPg to poliovirus RNA. Cell 59: 511–519

    Article  PubMed  CAS  Google Scholar 

  • Toh H, Hayashida H, Miyata T (1983) Sequence homology between retroviral reverse transcriptase and putative polymerases of hepatitis B virus and cauliflower mosaic virus. Nature 305: 827–829

    Article  PubMed  CAS  Google Scholar 

  • Tsurimoto T, Fujiyama A, Matsubara K (1987) Stable expression and replication of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA. Proc Natl Acad Sci USA 84: 444–448

    Article  PubMed  CAS  Google Scholar 

  • Tuttleman JS, Pugh JC, Summers JW (1986a) In vitro experimental infection of primary duck hepatocyte cultures with duck hepatitis B virus. J Virol 58: 17–25

    PubMed  CAS  Google Scholar 

  • Tuttleman JS, Pourcel C, Summers JW (1986b) Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 47: 451–46

    Article  PubMed  CAS  Google Scholar 

  • Varmus HE, Swanstrom R (1984) Replication of retroviruses. In: Weiss R, Teich N, Varmus HE, Coffin J (eds) RNA tumor viruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 369–512

    Google Scholar 

  • Varmus HE, Swanstrom R (1985) Replication of retroviruses. In: Weiss R, Teich N, Varmus HE, Coffin J (eds) RNA tumor viruses. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 75–134

    Google Scholar 

  • Weiser B, Ganem D, Seeger C, Varmus HE (1983) Closed circular viral DNA and asymmetric heterogeneous forms in livers from animals infected with ground squirrel hepatitis virus J Virol 48:1–9

    PubMed  CAS  Google Scholar 

  • Will H, Cattaneo R, Koch H, Darai G, Schaller H, Schellekens H, van Eer P, Deinhardt F (1982) Cloned HBV DNA causes hepatitis in chimpanzees. Nature 299: 740–742

    Article  PubMed  CAS  Google Scholar 

  • Will H, Reiser W, Weimer T, Pfaff E, Büscher M, Sprengel R, Cattaneo R, Schaller H (1987) Replication strategy of human hepatitis B virus. J Virol 61: 904–911

    PubMed  CAS  Google Scholar 

  • Wimmer E (1982) Genome-linked proteins of viruses. Cell 28: 199–201

    Article  PubMed  CAS  Google Scholar 

  • Wu T-T, Coates L, Aldrich CE, Summers J, Mason WS (1990) In hepatocytes infected with duck hepatitis B virus, the template for viral RNA synthesis is amplified by an intracellular pathway. Virology 175:255–261

    Article  PubMed  CAS  Google Scholar 

  • Yaginuma K, Shirakata Y, Kobayashi M, Koike K (1987) Hepatitis B virus (HBV) particles are produced in a cell culture system by transient expression of transfected HBV DNA. Proc Natl Acad Sci USA 84: 2678–2682

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology, Immunology and Parasitology, New York State College of Veterinary Medicine, Cornell University, 14853, Ithaca, NY, USA

    C. Seeger

  2. Department of Cell Biology, UNM Cancer Center, University of New Mexico, School of Medicine, 871311, Albuquerque, NM, USA

    J. Summers

  3. Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., 19111, Philadelphia, PA, USA

    W. S. Mason

Authors
  1. C. Seeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Summers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. S. Mason
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA, 19111, USA

    William S. Mason  & Christoph Seeger  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer-Verlag Berlin·Heidelberg

About this chapter

Cite this chapter

Seeger, C., Summers, J., Mason, W.S. (1991). Viral DNA Synthesis. In: Mason, W.S., Seeger, C. (eds) Hepadnaviruses. Current Topics in Microbiology and Immunology, vol 168. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76015-0_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-76015-0_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76017-4

  • Online ISBN: 978-3-642-76015-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation