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The interplay between host and viral genes in adenovirus gene expression

  • Ernst-Klenk-Preisvorlesung
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Summary

Only the left end of adenovirus DNA comprising the early E1A and E1B regions is required for transformation of rodent cells and for tumorigenicity in mice and rats. The E1A early region encodes a protein which probably indirectly through a cellular component controls mRNA expression from at least four other early regions at the transcriptional or post-transcriptional level.

Viral early proteins also combine with or control the expression of the cellular transplantation antigens to prepare the host cell for tumor rejection or alternatively to suppress the cellular immune response.

DNA replication of the viral genome requires three virus-coded proteins and two cellular proteins and is the first mammalian system where DNA can be efficiently replicated in an in vitro system.

Adenovirus late expression is also subject to cellular controls since the virus uses the host cell machinery for transcription and splicing.

A late translational control has also been identified which is mediated by a small virus coded RNA (VAI RNA) transcribed by the cellular polymerase III. The viral RNA is probably complexed with a cellular protein when excerting its effect.

All these control mechanisms, involving both viral and cellular genes, are now being dissected, and several of the molecules involved have been identified.

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References

  1. Akusjärvis G, Persson H (1981) Controls of RNA splicing and termination in the major late adenovirus transcription unit. Nature 292:420–426

    Google Scholar 

  2. Berget SM, Moore C, Sharp PA (1977) Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci USA 74:3171–3175

    Google Scholar 

  3. Bos JL, Polder L, Bernards R, Schrier P, van den Elsen P, van der Eb, AJ, van Ormondt H (1981) The 2.2 kb E1b mRNA of human Ad12 and Ad5 codes for two tumor antigens starting at different AUG triplets. Cell 27:121–131

    Google Scholar 

  4. Carlock LR, Jones NC (1981) Transformation-defective mutant of adenovirus type 5 containing a single altered E1a mRNA species. J Virol 40:657–664

    Google Scholar 

  5. Chow LT, Gelinas RE, Broker TR, Roberts RJ (1977) An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell 12:1–8

    Google Scholar 

  6. Gross FR, Darnell JE Jr (1983) Cycloheximide stimulates early adenovirus transcription if early gene expression is allowed before treatment. J Virol 45:683–692

    Google Scholar 

  7. Darnell JE Jr (1982) Variety in the level of gene control in eukaryotic cells. Nature 297:365–371

    Google Scholar 

  8. van Eekelen C, Buytels H, Linne T, Ohlsson R, Philipson L, van Venrooij W (1982) Detection of a cellular polypeptide associated with adenovirus-coded VA RNA using in vitro labeling of proteins cross-linked to RNA. Nucleic Acids Res 10:3039–3052

    Google Scholar 

  9. Feldman LT, Imperiale MJ, Nevins JR (1982) Activation of early adenovirus transcription by the herpesvirus immediate early gene: evidence for a common cellular control factor. Proc Natl Acad Sci USA 79:4952–4956

    Google Scholar 

  10. Hérissé J, Courtois G, Galibert F (1980) Nucleotide sequences of the EcoRI-D fragment of the adenovirus 2 genome. Nucleic Acids Res 8:2173–2191

    Google Scholar 

  11. Hérissé J, Galibert F (1981) Nucleotide sequence of the EcoRI E fragment of adenovirus 2 genome. Nucleic Acids Res 9:1229–1249

    Google Scholar 

  12. Hérissé J, Rigolet M, Dupont de Dinechin S, Galibert F (1981) Nucleotide sequence of adenovirus 2 DNA fragment encoding for the carboxylic region of the fiber protein and the entire E1 region. Nucleic Acids Res 9:4023–4042

    Google Scholar 

  13. Kämpe O, Bellgrau D, Hammerling U, Lind P, Pääbo S, Severinsson L, Peterson PA (1983) Complex formation of class I transplantation antigens and a viral glycoprotein. J Biol Chem 258:10594–10598

    Google Scholar 

  14. Katze MG, Persson H, Philipson L (1981) Control of adenovirus early gene expression: posttranscriptional control mediated by both viral and cellular gene products. Molec Cell Biol 1:807–813

    Google Scholar 

  15. Katze MG, Persson H, Philipson L (1982) A novel mRNA and a low molecular weight polypeptide encoded in the transforming region of adenovirus DNA. EMBO J 1:783–789

    Google Scholar 

  16. Katze MG, Persson H, Johansson BM, Philippson L (1983) Control of adenovirus gene expression: cellular gene products restrict expression of adenovirus host range mutants in nonpermissive cells. J Virol 46:50–59

    Google Scholar 

  17. Lichy JH, Field J, Horwitz MS, Hurwitz J (1982) Separation of the adenovirus terminal protein precursor from its associated DNA polymerase: role of both proteins in the initiation of adenovirus DNA replication. Proc Natl Acad Sci USA 79:5225–5229

    Google Scholar 

  18. Montell C, Fisher EF, Caruthers MH, Berk A (1982) Resolving the functions of overlapping viral genes by site-specific mutagenesis at a mRNA splice site. Nature 295:380–384

    Google Scholar 

  19. Nagata K, Guggenheimer RA, Enomoto T, Lichy JH, Hurwitz J (1982) Adenovirus DNA replication in vitro: identification of a host factor that stimulates synthesis of the preterminal protein dCMP complex. Proc Natl Acad Sci USA 79:6438–6442

    Google Scholar 

  20. Nevins JR, Jensen-Winkler J (1980) Regulation of early adenovirus transcription: a protein product of early region 2 specifically represses region 4 transcription. Proc Natl Acad Sci USA 77:1893–1897

    Google Scholar 

  21. Nevins JR (1981) Mechanism of activation of early viral transcription by the adenovirus E1A gene product. Cell 26:213–220

    Google Scholar 

  22. Ostrove JM, Rosenfeld P, Williams J, Kelly TJ Jr (1983) In vitro complementation as an assay for purification of adenovirus DNA replication proteins. Proc Natl Acad Sci USA 80:935–939

    Google Scholar 

  23. Persson H, Monstein HJ, Akusjärvi G, Philipson L (1981) Adenovirus early gene products may control viral mRNA accumulation and translation in vivo. Cell 23:485–496

    Google Scholar 

  24. Persson H, Philipson L (1982) Regulation of Adenovirus Gene Expression. Current topics in microbiology and immunology. Vol 97, Springer, Berlin Heidelberg New York, pp 152–203

    Google Scholar 

  25. Persson H, Katze MG, Philipson L (1982) Purification of a native membrane-associated adenovirus tumor antigen. J Virol 42:905–917

    Google Scholar 

  26. Ricciardi RP, Jones RL, Cepko CL, Sharp PA, Roberts BE (1981) Expression of early adenovirus genes requires a viral encoded acidic polypeptide. Proc Natl Acad Sci USA 78:6121–6125

    Google Scholar 

  27. Richardson WD, Westphal H (1981) A cascade of adenovirus early functions is required for expression of adeno-associated virus. Cell 27:133–141

    Google Scholar 

  28. Rinke J, Steitz JA (1982) Precursor molecules of both human 5S ribosomal RNA and transfer RNAs are bound by a cellular protein reactive with anti-La lupus antibodies. Cell 29:149–159

    Google Scholar 

  29. Schrier PI, Bernards R, Vaessen RTMJ, Houweling A, van der Eb AJ (1983) Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. Nature 305:771–775

    Google Scholar 

  30. Shaw AR, Ziff E (1980) Transcripts from the adenovirus-2 major late promoter yield a single early family of 3 coterminal mRNAs and five late families. Cell 22:905–916

    Google Scholar 

  31. Shaw AR, Ziff EB (1982) Selective inhibition of adenovirus type 2 early region II and III transcription by anisomycin block of protein synthesis. Molec Cell Biol 2:789–799

    Google Scholar 

  32. Signäs C, Katze MG, Persson H, Philipson L (1982) An adenovirus glycoprotein binds heavy chains of class I transplantation antigens from man and mouse. Nature 299:175–178

    Google Scholar 

  33. Solnick D, Anderson MA (1982) Transformation-deficient adenovirus mutant defective in expression of region 1A but not region 1B. J Virol 42:106–113

    Google Scholar 

  34. Thimmappaya B, Weinberger C, Schneider RJ, Shenk T (1982) Adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. Cell 31:543–551

    Google Scholar 

  35. Wilson MC, Fraser NW, Darnell JE (1979) Mapping of RNA initiation sites by high doses of UV irradiation: evidence for three independent promoters within the left 11% of the ad-2 genome. Virology 94:175–184

    Google Scholar 

  36. Zinkernagel RM, Doherty PC (1979) MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol 27:51–177

    Google Scholar 

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Authors and Affiliations

  1. Europäisches Laboratorium für Molekular-Biologie Heidelberg, Germany

    L. Philipson

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  1. L. Philipson
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Ernst Klenk Lecture, November 4, 1983

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Philipson, L. The interplay between host and viral genes in adenovirus gene expression. Klin Wochenschr 62, 433–440 (1984). https://doi.org/10.1007/BF01726903

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  • DOI: https://doi.org/10.1007/BF01726903

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