Abstract
H2dl808 is a deletion mutant of adenovirus type 2 lacking most of transcriptional early region E4. In most normal adenovirus host cells this virus displayed a complex mutant phenotype that included a dramatic reduction in the level of cytoplasmic late RNA, a corresponding defect in late protein synthesis, and a 5- to 10-fold defect in viral DNA accumulation. H5dl1004 is a deletion mutant of adenovirus type 5 that also lacks a portion of E4. It exhibited a reduction in levels of cytoplasmic late RNAs that was somewhat less severe than that of H2dl808 and a corresponding late protein synthetic defect but no defect in the production of viral DNA. In addition to the defect in the accumulation of late cytoplasmic mRNAs, HeLa cells infected by either H2dl808 or H5dl1004 showed substantially reduced levels of viral RNAs in their nuclei at late times after infection. Both mature mRNAs and apparent mRNA precursors were affected. The late transcription rates of the deletion mutant viruses were similar to that of wild-type virus. These results suggest that the underaccumulation of RNA in H2dl808- and H5dl1004-infected cells is caused by a reduction in the stability of viral RNA in the nucleus, and they implicate E4 products in a novel aspect of the regulation of viral gene expression.
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- Babich A., Feldman L. T., Nevins J. R., Darnell J. E., Jr, Weinberger C. Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination. Mol Cell Biol. 1983 Jul;3(7):1212–1221. doi: 10.1128/mcb.3.7.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Babiss L. E., Ginsberg H. S., Darnell J. E., Jr Adenovirus E1B proteins are required for accumulation of late viral mRNA and for effects on cellular mRNA translation and transport. Mol Cell Biol. 1985 Oct;5(10):2552–2558. doi: 10.1128/mcb.5.10.2552. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beltz G. A., Flint S. J. Inhibition of HeLa cell protein synthesis during adenovirus infection. Restriction of cellular messenger RNA sequences to the nucleus. J Mol Biol. 1979 Jun 25;131(2):353–373. doi: 10.1016/0022-2836(79)90081-0. [DOI] [PubMed] [Google Scholar]
- Berget S. M., Moore C., Sharp P. A. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3171–3175. doi: 10.1073/pnas.74.8.3171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berk A. J., Lee F., Harrison T., Williams J., Sharp P. A. Pre-early adenovirus 5 gene product regulates synthesis of early viral messenger RNAs. Cell. 1979 Aug;17(4):935–944. doi: 10.1016/0092-8674(79)90333-7. [DOI] [PubMed] [Google Scholar]
- Bridge E., Ketner G. Redundant control of adenovirus late gene expression by early region 4. J Virol. 1989 Feb;63(2):631–638. doi: 10.1128/jvi.63.2.631-638.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Challberg S. S., Ketner G. Deletion mutants of adenovirus 2: isolation and initial characterization of virus carrying mutations near the right end of the viral genome. Virology. 1981 Oct 15;114(1):196–209. doi: 10.1016/0042-6822(81)90265-8. [DOI] [PubMed] [Google Scholar]
- Cutt J. R., Shenk T., Hearing P. Analysis of adenovirus early region 4-encoded polypeptides synthesized in productively infected cells. J Virol. 1987 Feb;61(2):543–552. doi: 10.1128/jvi.61.2.543-552.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Freyer G. A., Katoh Y., Roberts R. J. Characterization of the major mRNAs from adenovirus 2 early region 4 by cDNA cloning and sequencing. Nucleic Acids Res. 1984 Apr 25;12(8):3503–3519. doi: 10.1093/nar/12.8.3503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GREEN M., DAESCH G. E. Biochemical studies on adenovirus multiplication. II. Kinetics of nucleic acid and protein synthesis in suspension cultures. Virology. 1961 Feb;13:169–176. doi: 10.1016/0042-6822(61)90051-4. [DOI] [PubMed] [Google Scholar]
- Groudine M., Peretz M., Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. doi: 10.1128/mcb.1.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halbert D. N., Cutt J. R., Shenk T. Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff. J Virol. 1985 Oct;56(1):250–257. doi: 10.1128/jvi.56.1.250-257.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
- Hérissé J., Rigolet M., de Dinechin S. D., Galibert F. Nucleotide sequence of adenovirus 2 DNA fragment encoding for the carboxylic region of the fiber protein and the entire E4 region. Nucleic Acids Res. 1981 Aug 25;9(16):4023–4042. doi: 10.1093/nar/9.16.4023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones N., Shenk T. An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3665–3669. doi: 10.1073/pnas.76.8.3665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kovesdi I., Reichel R., Nevins J. R. Identification of a cellular transcription factor involved in E1A trans-activation. Cell. 1986 Apr 25;45(2):219–228. doi: 10.1016/0092-8674(86)90386-7. [DOI] [PubMed] [Google Scholar]
- Kwong A. D., Frenkel N. Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1926–1930. doi: 10.1073/pnas.84.7.1926. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Persson H., Philipson L. Regulation of adenovirus gene expression. Curr Top Microbiol Immunol. 1982;97:157–203. doi: 10.1007/978-3-642-68318-3_4. [DOI] [PubMed] [Google Scholar]
- Pilder S., Moore M., Logan J., Shenk T. The adenovirus E1B-55K transforming polypeptide modulates transport or cytoplasmic stabilization of viral and host cell mRNAs. Mol Cell Biol. 1986 Feb;6(2):470–476. doi: 10.1128/mcb.6.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ricciardi R. P., Jones R. L., Cepko C. L., Sharp P. A., Roberts B. E. Expression of early adenovirus genes requires a viral encoded acidic polypeptide. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6121–6125. doi: 10.1073/pnas.78.10.6121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarnow P., Hearing P., Anderson C. W., Halbert D. N., Shenk T., Levine A. J. Adenovirus early region 1B 58,000-dalton tumor antigen is physically associated with an early region 4 25,000-dalton protein in productively infected cells. J Virol. 1984 Mar;49(3):692–700. doi: 10.1128/jvi.49.3.692-700.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarnow P., Hearing P., Anderson C. W., Reich N., Levine A. J. Identification and characterization of an immunologically conserved adenovirus early region 11,000 Mr protein and its association with the nuclear matrix. J Mol Biol. 1982 Dec 15;162(3):565–583. doi: 10.1016/0022-2836(82)90389-8. [DOI] [PubMed] [Google Scholar]
- Tigges M. A., Raskas H. J. Expression of adenovirus-2 early region 4: assignment of the early region 4 polypeptides to their respective mRNAs, using in vitro translation. J Virol. 1982 Dec;44(3):907–921. doi: 10.1128/jvi.44.3.907-921.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Virtanen A., Gilardi P., Näslund A., LeMoullec J. M., Pettersson U., Perricaudet M. mRNAs from human adenovirus 2 early region 4. J Virol. 1984 Sep;51(3):822–831. doi: 10.1128/jvi.51.3.822-831.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinberg D. H., Ketner G. A cell line that supports the growth of a defective early region 4 deletion mutant of human adenovirus type 2. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5383–5386. doi: 10.1073/pnas.80.17.5383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinberg D. H., Ketner G. Adenoviral early region 4 is required for efficient viral DNA replication and for late gene expression. J Virol. 1986 Mar;57(3):833–838. doi: 10.1128/jvi.57.3.833-838.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yoder S. S., Berget S. M. Role of adenovirus type 2 early region 4 in the early-to-late switch during productive infection. J Virol. 1986 Nov;60(2):779–781. doi: 10.1128/jvi.60.2.779-781.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]