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. 1985 Dec;56(3):821–829. doi: 10.1128/jvi.56.3.821-829.1985

Similar regulation of the synthesis of adenovirus fiber and of simian virus 40-specific proteins encoded by the helper-defective Ad2+SV40 hybrid viruses Ad2+ND5 and Ad2+ND4del.

U Klockmann, D F Klessig, W Deppert
PMCID: PMC252653  PMID: 2999437

Abstract

Human adenoviruses fail to multiply effectively in monkey cells. The block to the replication of these viruses can be overcome by coinfection with simian virus 40 (SV40) or when part of the SV40 genome is integrated into and expressed as part of the adenovirus type 2 (Ad2) genome, as occurs in several Ad2+SV40 hybrid viruses, such as Ad2+ND1, Ad2+ND2, and Ad2+ND4. The SV40 helper-defective Ad2+SV40 hybrid viruses Ad2+ND5 and Ad2+ND4del were analyzed to determine why they are unable to grow efficiently in monkey cells even though they contain the appropriate SV40 genetic information. Characterization of the Ad2+ND5-SV40-specific 42,000-molecular-weight (42K) protein revealed that this protein is closely related, but not identical, to the SV40-specific 42K protein of the SV40 helper-competent Ad2+ND2 hybrid virus. Although the minor differences between these proteins may be sufficient to account for the poor growth of Ad2+ND5 in monkey cells, the most striking difference between helper-competent Ad2+ND2 and helper-defective Ad2+ND5 is in the production of the SV40-specific protein after infection of monkey cells. Whereas synthesis of the SV40-specific proteins of Ad2+ND2 is very similar in human and in monkey cells, production of the 42K protein of Ad2+ND5 is dramatically reduced in monkey cells compared with human cells. Similarly, the synthesis of the SV40-specific proteins of Ad2+ND4del is markedly reduced in monkey cells. Thus, it is likely that both Ad2+ND5 and Ad2+ND4del are helper defective because of a block in the production of their SV40-specific proteins rather than because their SV40-specific proteins are nonfunctional. This block, like the block to adenovirus fiber synthesis, is overcome by coinfection with SV40, with helper-competent hybrid viruses, or with host range mutants of adenoviruses. This suggests that the synthesis of fiber and the synthesis of SV40-specific proteins are similarly regulated in Ad2+SV40 hybrid viruses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson C. W., Hardy M. M., Dunn J. J., Klessig D. F. Independent, spontaneous mutants of adenovirus type 2-simian virus 40 hybrid Ad2+ND3 that grow efficiently in monkey cells possess indentical mutations in the adenovirus type 2 DNA-binding protein gene. J Virol. 1983 Oct;48(1):31–39. doi: 10.1128/jvi.48.1.31-39.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson C. W. Spontaneous mutants of the adenovirus-simian virus 40 hybrid, Ad2+ND3, that grow efficiently in monkey cells. Virology. 1981 May;111(1):263–269. doi: 10.1016/0042-6822(81)90670-x. [DOI] [PubMed] [Google Scholar]
  3. Anderson K. P., Klessig D. F. Altered mRNA splicing in monkey cells abortively infected with human adenovirus may be responsible for inefficient synthesis of the virion fiber polypeptide. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4023–4027. doi: 10.1073/pnas.81.13.4023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anderson K. P., Klessig D. F. Posttranscriptional block to synthesis of a human adenovirus capsid protein in abortively infected monkey cells. J Mol Appl Genet. 1983;2(1):31–43. [PubMed] [Google Scholar]
  5. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  6. Cole C. N., Crawford L. V., Berg P. Simian virus 40 mutants with deletions at the 3' end of the early region are defective in adenovirus helper function. J Virol. 1979 Jun;30(3):683–691. doi: 10.1128/jvi.30.3.683-691.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crawford L., Harlow E. Uniform nomenclature for monoclonal antibodies directed against virus-coded proteins of simian virus 40 and polyoma virus. J Virol. 1982 Feb;41(2):709–709. doi: 10.1128/jvi.41.2.709-709.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deppert W., Gurney E. G., Harrison R. O. Monoclonal antibodies against simian virus 40 tumor antigens: analysis of antigenic binding sites, using adenovirus type 2-simian virus 40 hybrid viruses. J Virol. 1981 Jan;37(1):478–482. doi: 10.1128/jvi.37.1.478-482.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Deppert W., Pates R. Cell surface location of simian virus 40-specific proteins on HeLa cells infected with adenovirus type 2-simian virus 40 hybrid viruses Ad2+ND1 and Ad2+ND2. J Virol. 1979 Aug;31(2):522–536. doi: 10.1128/jvi.31.2.522-536.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Deppert W., Walter G. Domains of simian virus 40 large T-antigen exposed on the cell surface. Virology. 1982 Oct 15;122(1):56–70. doi: 10.1016/0042-6822(82)90377-4. [DOI] [PubMed] [Google Scholar]
  11. Deppert W., Walter G., Linke H. Simian virus 40 tumor-specific proteins: subcellular distribution and metabolic stability in HeLa cells infected with nondefective adenovirus type 2-simian virus 40 hybrid viruses. J Virol. 1977 Mar;21(3):1170–1186. doi: 10.1128/jvi.21.3.1170-1186.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fey G., Lewis J. B., Grodzicker T., Bothwell A. Characterization of a fused protein specified by the adenovirus type 2-simian virus 40 hybrid Ad2+ND1 dp2. J Virol. 1979 Apr;30(1):201–217. doi: 10.1128/jvi.30.1.201-217.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gibson W. Polyoma virus proteins: a description of the structural proteins of the virion based on polyacrylamide gel electrophoresis and peptide analysis. Virology. 1974 Dec;62(2):319–336. doi: 10.1016/0042-6822(74)90395-x. [DOI] [PubMed] [Google Scholar]
  14. Grodzicker T., Anderson C., Sharp P. A., Sambrook J. Conditional lethal mutants of adenovirus 2-simian virus 40 hybrids. I. Host range mutants of Ad2+ND1. J Virol. 1974 Jun;13(6):1237–1244. doi: 10.1128/jvi.13.6.1237-1244.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gurney E. G., Harrison R. O., Fenno J. Monoclonal antibodies against simian virus 40 T antigens: evidence for distinct sublcasses of large T antigen and for similarities among nonviral T antigens. J Virol. 1980 Jun;34(3):752–763. doi: 10.1128/jvi.34.3.752-763.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Henry P. H., Schnipper L. E., Samaha R. J., Crumpacker C. S., Lewis A. M., Jr, Levine A. S. Studies of nondefective adenovirus 2-simian virus 40 hybrid viruses. VI. Characterization of the DNA from five nondefective hybrid viruses. J Virol. 1973 May;11(5):665–671. doi: 10.1128/jvi.11.5.665-671.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johnston J. M., Anderson K. P., Klessig D. F. Partial block to transcription of human adenovirus type 2 late genes in abortively infected monkey cells. J Virol. 1985 Nov;56(2):378–385. doi: 10.1128/jvi.56.2.378-385.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kelly T. J., Jr, Lewis A. M., Jr Use of nondefective adenovirus-simian virus 40 hybrids for mapping the simian virus 40 genome. J Virol. 1973 Sep;12(3):643–652. doi: 10.1128/jvi.12.3.643-652.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Khoury G., Alwine J., Goldman N., Gruss P., Jay G. New chimeric splice junction in adenovirus type 2-simian virus 40 hybrid viral mRNA. J Virol. 1980 Oct;36(1):143–151. doi: 10.1128/jvi.36.1.143-151.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Klessig D. F., Anderson C. W. Block to multiplication of adenovirus serotype 2 in monkey cells. J Virol. 1975 Dec;16(6):1650–1668. doi: 10.1128/jvi.16.6.1650-1668.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Klessig D. F., Chow L. T. Incomplete splicing and deficient accumulation of the fiber messenger RNA in monkey cells infected by human adenovirus type 2. J Mol Biol. 1980 May 15;139(2):221–242. doi: 10.1016/0022-2836(80)90306-x. [DOI] [PubMed] [Google Scholar]
  22. Klessig D. F., Grodzicker T. Mutations that allow human Ad2 and Ad5 to express late genes in monkey cells map in the viral gene encoding the 72K DNA binding protein. Cell. 1979 Aug;17(4):957–966. doi: 10.1016/0092-8674(79)90335-0. [DOI] [PubMed] [Google Scholar]
  23. Klessig D. F., Hassell J. A. Characterization of a variant of human adenovirus type 2 which multiples efficiently in simian cells. J Virol. 1978 Dec;28(3):945–956. doi: 10.1128/jvi.28.3.945-956.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Klessig D. F. Isolation of a variant of human adenovirus serotype 2 that multiplies efficiently on monkey cells. J Virol. 1977 Mar;21(3):1243–1246. doi: 10.1128/jvi.21.3.1243-1246.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  26. Lebowitz P., Kelly T. J., Jr, Nathans D., Lee T. N., Lewis A. M., Jr A colinear map relating the simian virus 40 (SV40) DNA segments of six adenovirus-SV40 hybrids to the DNA fragments produced by restriction endonuclease cleavage of SV40 DNA. Proc Natl Acad Sci U S A. 1974 Feb;71(2):441–445. doi: 10.1073/pnas.71.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lewis A. M., Jr, Levin M. J., Wiese W. H., Crumpacker C. S., Henry P. H. A nondefective (competent) adenovirus-SV40 hybrid isolated from the AD.2-SV40 hybrid population. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1128–1135. doi: 10.1073/pnas.63.4.1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lewis A. M., Jr, Levine A. S., Crumpacker C. S., Levin M. J., Samaha R. J., Henry P. H. Studies of nondefective adenovirus 2-simian virus 40 hybrid viruses. V. Isolation of additional hybrids which differ in their simian virus 40-specific biological properties. J Virol. 1973 May;11(5):655–664. doi: 10.1128/jvi.11.5.655-664.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lewis A. M., Jr, Westphal H. The adenovirus type 2-simian virus 40 hybrid virus Ad2+ND4 requires deletion variants to grow in monkey cells. J Virol. 1983 Aug;47(2):344–353. doi: 10.1128/jvi.47.2.344-353.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mann K., Hunter T., Walter G., Linke H. Evidence for simian virus 40 (SV40) coding of SV40 T-antigen and the SV40-specific proteins in HeLa cells infected with nondefective adenovirus type 2-SV40 hybrid viruses. J Virol. 1977 Oct;24(1):151–169. doi: 10.1128/jvi.24.1.151-169.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Morrow J. F., Berg P. Cleavage of Simian virus 40 DNA at a unique site by a bacterial restriction enzyme. Proc Natl Acad Sci U S A. 1972 Nov;69(11):3365–3369. doi: 10.1073/pnas.69.11.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Morrow J. F., Berg P., Kelly T. J., Jr, Lewis A. M., Jr Mapping of simian virus 40 early functions on the viral chromosome. J Virol. 1973 Sep;12(3):653–658. doi: 10.1128/jvi.12.3.653-658.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. RABSON A. S., O'CONOR G. T., BEREZESKY I. K., PAUL F. J. ENHANCEMENT OF ADENOVIRUS GROWTH IN AFRICAN GREEN MONKEY KIDNEY CELL CULTURES BY SV40. Proc Soc Exp Biol Med. 1964 May;116:187–190. doi: 10.3181/00379727-116-29197. [DOI] [PubMed] [Google Scholar]
  34. Rice S. A., Klessig D. F. The function(s) provided by the adenovirus-specified, DNA-binding protein required for viral late gene expression is independent of the role of the protein in viral DNA replication. J Virol. 1984 Jan;49(1):35–49. doi: 10.1128/jvi.49.1.35-49.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Scheidtmann K. H., Kaiser A., Carbone A., Walter G. Phosphorylation of threonine in the proline-rich carboxy-terminal region of simian virus 40 large T antigen. J Virol. 1981 Apr;38(1):59–69. doi: 10.1128/jvi.38.1.59-69.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Silverman L., Anderson K. P., Klessig D. F. Synthesis of the Ad2+ND5-specified 42K protein is regulated posttranscriptionally in abortively infected monkey cells. J Virol. 1985 Dec;56(3):814–820. doi: 10.1128/jvi.56.3.814-820.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Van Heuverswyn H., Cole C., Berg P., Fiers W. Nucleotide sequence analysis of two simian virus 40 mutants with deletions in the region coding for the carboxyl terminus of the T antigen. J Virol. 1979 Jun;30(3):936–941. doi: 10.1128/jvi.30.3.936-941.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Walter G., Martin H. Simian virus 40-specific proteins in HeLa cells infected with nondefective adenovirus 2-simian virus 40 hybrid viruses. J Virol. 1975 Nov;16(5):1236–1247. doi: 10.1128/jvi.16.5.1236-1247.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Walter G., Scheidtmann K. H., Carbone A., Laudano A. P., Doolittle R. F. Antibodies specific for the carboxy- and amino-terminal regions of simian virus 40 large tumor antigen. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5197–5200. doi: 10.1073/pnas.77.9.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Westphal H. Genomic arrangement of an adenovirus-simian virus 40 hybrid virus, Ad2+ND4del. J Virol. 1981 Nov;40(2):526–532. doi: 10.1128/jvi.40.2.526-532.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Westphal H., Lai S. P., Lawrence C., Hunter T., Walter G. Mosaic adenovirus-SV40 RNA specified by the non-defective hybrid virus Ad2+ND4. J Mol Biol. 1979 May 25;130(3):337–351. doi: 10.1016/0022-2836(79)90545-x. [DOI] [PubMed] [Google Scholar]

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