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. 1986 Nov;60(2):363–368. doi: 10.1128/jvi.60.2.363-368.1986

Suppression of the translation defect phenotype specific for a virus-associated RNA-deficient adenovirus mutant in monkey cells by simian virus 40.

S Subramanian, R A Bhat, M K Rundell, B Thimmappaya
PMCID: PMC288901  PMID: 3021970

Abstract

Human cells infected with adenovirus type 2 (Ad2) or Ad5 require VAI RNA for efficient translation of viral mRNAs at late times after infection. The Ad5 mutant dl-sub720 synthesized neither virus-associated I (VAI) nor VAII RNAs, and infection of human cells with this mutant resulted in reduced virion polypeptide synthesis. Infection of monkey cells with this mutant also resulted in drastic reduction of polypeptide synthesis compared with wild-type (WT) adenovirus infections. Steady-state levels of hexon-specific mRNA were found to be comparable in WT- and mutant-infected monkey cells. The in vitro translation experiments showed that double-mutant- and WT-infected cells contained comparable levels of translatable hexon mRNA (and other adenovirus late mRNAs), suggesting that the severe inhibition of hexon protein synthesis in the VA mutant involves a translation block. Preinfection of monkey cells with simian virus 40 fully restored the efficient translation of this mRNA in the VA mutant infections to the level observed in WT-infected cultures. These results raise the possibility that simian virus 40 may encode or induce factors that suppress the translation block that occurs during adenovirus infections in the absence of the VA RNAs.

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Selected References

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  1. Akusjärvi G., Mathews M. B., Andersson P., Vennström B., Pettersson U. Structure of genes for virus-associated RNAI and RNAII of adenovirus type 2. Proc Natl Acad Sci U S A. 1980 May;77(5):2424–2428. doi: 10.1073/pnas.77.5.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alwine J. C., Khoury G. Simian virus 40-associated small RNA: mapping on the simian virus 40 genome and characterization of its synthesis. J Virol. 1980 Dec;36(3):701–708. doi: 10.1128/jvi.36.3.701-708.1980. [DOI] [PMC free article] [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. Baum S. G., Horwitz M. S., Maizel J. V., Jr Studies of the mechanism of enhancement of human adenovirus infection in monkey cells by simian virus 40. J Virol. 1972 Aug;10(2):211–219. doi: 10.1128/jvi.10.2.211-219.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhat R. A., Domer P. H., Thimmappaya B. Structural requirements of adenovirus VAI RNA for its translation enhancement function. Mol Cell Biol. 1985 Jan;5(1):187–196. doi: 10.1128/mcb.5.1.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bhat R. A., Thimmappaya B. Adenovirus mutants with DNA sequence perturbations in the intragenic promoter of VAI RNA gene allow the enhanced transcription of VAII RNA gene in HeLa cells. Nucleic Acids Res. 1984 Oct 11;12(19):7377–7388. doi: 10.1093/nar/12.19.7377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bhat R. A., Thimmappaya B. Construction and analysis of additional adenovirus substitution mutants confirm the complementation of VAI RNA function by two small RNAs encoded by Epstein-Barr virus. J Virol. 1985 Dec;56(3):750–756. doi: 10.1128/jvi.56.3.750-756.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bhat R. A., Thimmappaya B. Two small RNAs encoded by Epstein-Barr virus can functionally substitute for the virus-associated RNAs in the lytic growth of adenovirus 5. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4789–4793. doi: 10.1073/pnas.80.15.4789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cepko C. L., Sharp P. A. Analysis of Ad5 hexon and 100K ts mutants using conformation-specific monoclonal antibodies. Virology. 1983 Aug;129(1):137–154. doi: 10.1016/0042-6822(83)90402-6. [DOI] [PubMed] [Google Scholar]
  10. Farber M. S., Baum S. G. Transcription of adenovirus RNA in permissive and nonpermissive infections. J Virol. 1978 Jul;27(1):136–148. doi: 10.1128/jvi.27.1.136-148.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Farrell P. J., Balkow K., Hunt T., Jackson R. J., Trachsel H. Phosphorylation of initiation factor elF-2 and the control of reticulocyte protein synthesis. Cell. 1977 May;11(1):187–200. doi: 10.1016/0092-8674(77)90330-0. [DOI] [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. Francoeur A. M., Mathews M. B. Interaction between VA RNA and the lupus antigen La: formation of a ribonucleoprotein particle in vitro. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6772–6776. doi: 10.1073/pnas.79.22.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hashimoto K., Nakajima K., Oda K., Shimojo H. Complementation of translational defect for growth of human adenovirus type 2 in Simian cells by a Simian virus 40-induced factor. J Mol Biol. 1973 Dec 5;81(2):207–223. doi: 10.1016/0022-2836(73)90190-3. [DOI] [PubMed] [Google Scholar]
  17. Hunter T., Hunt T., Jackson R. J., Robertson H. D. The characteristics of inhibition of protein synthesis by double-stranded ribonucleic acid in reticulocyte lysates. J Biol Chem. 1975 Jan 25;250(2):409–417. [PubMed] [Google Scholar]
  18. 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]
  19. Katze M. G., Chen Y. T., Krug R. M. Nuclear-cytoplasmic transport and VAI RNA-independent translation of influenza viral messenger RNAs in late adenovirus-infected cells. Cell. 1984 Jun;37(2):483–490. doi: 10.1016/0092-8674(84)90378-7. [DOI] [PubMed] [Google Scholar]
  20. Kitajewski J., Schneider R. J., Safer B., Munemitsu S. M., Samuel C. E., Thimmappaya B., Shenk T. Adenovirus VAI RNA antagonizes the antiviral action of interferon by preventing activation of the interferon-induced eIF-2 alpha kinase. Cell. 1986 Apr 25;45(2):195–200. doi: 10.1016/0092-8674(86)90383-1. [DOI] [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. Lebleu B., Sen G. C., Shaila S., Cabrer B., Lengyel P. Interferon, double-stranded RNA, and protein phosphorylation. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3107–3111. doi: 10.1073/pnas.73.9.3107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lerner M. R., Andrews N. C., Miller G., Steitz J. A. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1981 Feb;78(2):805–809. doi: 10.1073/pnas.78.2.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lerner M. R., Boyle J. A., Hardin J. A., Steitz J. A. Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science. 1981 Jan 23;211(4480):400–402. doi: 10.1126/science.6164096. [DOI] [PubMed] [Google Scholar]
  25. Lucas J. J., Ginsberg H. S. Transcription and transport of virus-specific ribonucleic acids in African green monkey kidney cells abortively infected with type 2 adenovirus. J Virol. 1972 Dec;10(6):1109–1117. doi: 10.1128/jvi.10.6.1109-1117.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miyamoto N. G., Jacobs B. L., Samuel C. E. Mechanism of interferon action. Effect of double-stranded RNA and the 5'-O-monophosphate form of 2',5'-oligoadenylate on the inhibition of reovirus mRNA translation in vitro. J Biol Chem. 1983 Dec 25;258(24):15232–15237. [PubMed] [Google Scholar]
  27. O'Malley R. P., Mariano T. M., Siekierka J., Mathews M. B. A mechanism for the control of protein synthesis by adenovirus VA RNAI. Cell. 1986 Feb 14;44(3):391–400. doi: 10.1016/0092-8674(86)90460-5. [DOI] [PubMed] [Google Scholar]
  28. Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Rave N., Crkvenjakov R., Boedtker H. Identification of procollagen mRNAs transferred to diazobenzyloxymethyl paper from formaldehyde agarose gels. Nucleic Acids Res. 1979 Aug 10;6(11):3559–3567. doi: 10.1093/nar/6.11.3559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Reich P. R., Forget B. G., Weissman S. M. RNA of low molecular weight in KB cells infected with adenovirus type 2. J Mol Biol. 1966 Jun;17(2):428–439. doi: 10.1016/s0022-2836(66)80153-5. [DOI] [PubMed] [Google Scholar]
  32. Reichel P. A., Merrick W. C., Siekierka J., Mathews M. B. Regulation of a protein synthesis initiation factor by adenovirus virus-associated RNA. Nature. 1985 Jan 17;313(5999):196–200. doi: 10.1038/313196a0. [DOI] [PubMed] [Google Scholar]
  33. Roberts W. K., Hovanessian A., Brown R. E., Clemens M. J., Kerr I. M. Interferon-mediated protein kinase and low-molecular-weight inhibitor of protein synthesis. Nature. 1976 Dec 2;264(5585):477–480. doi: 10.1038/264477a0. [DOI] [PubMed] [Google Scholar]
  34. Rosen H., Knoller S., Kaempfer R. Messenger ribonucleic acid specificity in the inhibition of eukaryotic translation by double-stranded ribonucleic acid. Biochemistry. 1981 May 26;20(11):3011–3020. doi: 10.1021/bi00514a004. [DOI] [PubMed] [Google Scholar]
  35. Schneider R. J., Safer B., Munemitsu S. M., Samuel C. E., Shenk T. Adenovirus VAI RNA prevents phosphorylation of the eukaryotic initiation factor 2 alpha subunit subsequent to infection. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4321–4325. doi: 10.1073/pnas.82.13.4321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schneider R. J., Weinberger C., Shenk T. Adenovirus VAI RNA facilitates the initiation of translation in virus-infected cells. Cell. 1984 May;37(1):291–298. doi: 10.1016/0092-8674(84)90325-8. [DOI] [PubMed] [Google Scholar]
  37. Siekierka J., Mariano T. M., Reichel P. A., Mathews M. B. Translational control by adenovirus: lack of virus-associated RNAI during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1959–1963. doi: 10.1073/pnas.82.7.1959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Singh K., Carey M., Saragosti S., Botchan M. Expression of enhanced levels of small RNA polymerase III transcripts encoded by the B2 repeats in simian virus 40-transformed mouse cells. Nature. 1985 Apr 11;314(6011):553–556. doi: 10.1038/314553a0. [DOI] [PubMed] [Google Scholar]
  39. Söderlund H., Pettersson U., Vennström B., Philipson L., Mathews M. B. A new species of virus-coded low molecular weight RNA from cells infected with adenovirus type 2. Cell. 1976 Apr;7(4):585–593. doi: 10.1016/0092-8674(76)90209-9. [DOI] [PubMed] [Google Scholar]
  40. Takemoto K. K., Kirschstein R. L., Habel K. Mutants of simian virus 40 differing in plaque size, oncogenicity, and heat sensitivity. J Bacteriol. 1966 Oct;92(4):990–994. doi: 10.1128/jb.92.4.990-994.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Thimmappaya B., Weinberger C., Schneider R. J., Shenk T. Adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. Cell. 1982 Dec;31(3 Pt 2):543–551. doi: 10.1016/0092-8674(82)90310-5. [DOI] [PubMed] [Google Scholar]
  42. Tornow J., Cole C. N. Nonviable mutants of simian virus 40 with deletions near the 3' end of gene A define a function for large T antigen required after onset of viral DNA replication. J Virol. 1983 Sep;47(3):487–494. doi: 10.1128/jvi.47.3.487-494.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Weinmann R., Brendler T. G., Raskas H. J., Roeder R. G. Low molecular weight viral RNAs transcribed by RNA polymerase III during adenovirus 2 infection. Cell. 1976 Apr;7(4):557–566. doi: 10.1016/0092-8674(76)90206-3. [DOI] [PubMed] [Google Scholar]
  44. Whitaker-Dowling P., Youngner J. S. Characterization of a specific kinase inhibitory factor produced by vaccinia virus which inhibits the interferon-induced protein kinase. Virology. 1984 Aug;137(1):171–181. doi: 10.1016/0042-6822(84)90020-5. [DOI] [PubMed] [Google Scholar]
  45. Zilberstein A., Federman P., Shulman L., Revel M. Specific phosphorylation in vitro of a protein associated with ribosomes of interferon-treated mouse L cells. FEBS Lett. 1976 Sep 15;68(1):119–124. doi: 10.1016/0014-5793(76)80418-8. [DOI] [PubMed] [Google Scholar]

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