title: Adenovirus late-phase infection is controlled by a novel L4 promoter.
abstract: During human adenovirus 5 infection, a temporal cascade of gene expression leads ultimately to the production of large amounts of the proteins needed to construct progeny virions. However, the mechanism for the activation of the major late gene that encodes these viral structural proteins has not been well understood. We show here that two key positive regulators of the major late gene, L4-22K and L4-33K, previously thought to be expressed under the control of the major late promoter itself, initially are expressed from a novel promoter that is embedded within the major late gene and dedicated to their expression. This L4 promoter is required for late gene expression and is activated by a combination of viral protein activators produced during the infection, including E1A, E4 Orf3, and the intermediate-phase protein IVa2, and also by viral genome replication. This new understanding redraws the long-established view of how adenoviral gene expression patterns are controlled and offers new ways to manipulate that gene expression cascade for adenovirus vector applications.
authors.affiliation: Department of Biological Sciences, University of Warwick, Gibbet Hill Rd., Coventry CV4 7AL, United Kingdom.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Morris
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Scott
authors.forename: Keith N
authors.initials: KN
authors.lastname: Leppard
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics* / Q000472:pathogenicity*; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins
references.citation: J Cell Biol. 1995 Oct;131(1):45-56
references.pmid: 7559785
references.citation: J Virol. 2004 Feb;78(4):1782-91
references.pmid: 14747543
references.citation: Cell. 1978 Oct;15(2):497-510
references.pmid: 719751
references.citation: Virology. 1979 Apr 15;94(1):175-84
references.pmid: 442530
references.citation: J Biol Chem. 2006 Dec 1;281(48):36510-7
references.pmid: 17028184
references.citation: Virology. 1983 Jul 30;128(2):480-4
references.pmid: 6310869
references.citation: J Virol. 1996 Mar;70(3):1396-405
references.pmid: 8627656
references.citation: Genes Dev. 1996 Jan 15;10(2):196-207
references.pmid: 8566753
references.citation: J Virol. 2007 Apr;81(8):4264-71
references.pmid: 17287283
references.citation: J Thromb Haemost. 2006 Jun;4(6):1218-1225
references.pmid: 16706963
references.citation: J Biol Chem. 1992 Dec 15;267(35):25457-65
references.pmid: 1460040
references.citation: J Virol. 1996 Jul;70(7):4805-10
references.pmid: 8676512
references.citation: Cell. 1980 Dec;22(3):905-16
references.pmid: 7460018
references.citation: Cell. 1979 Aug;17(4):935-44
references.pmid: 487437
references.citation: Nucleic Acids Res. 1992 Aug 11;20(15):3881-9
references.pmid: 1508674
references.citation: J Virol. 2007 Feb;81(3):1327-38
references.pmid: 17093188
references.citation: J Gen Virol. 1999 Apr;80 ( Pt 4):997-1008
references.pmid: 10211970
references.citation: J Virol. 2008 Aug;82(15):7325-35
references.pmid: 18480450
references.citation: J Virol. 1989 Feb;63(2):631-8
references.pmid: 2911117
references.citation: Nature. 1981 Mar 12;290(5802):113-8
references.pmid: 7207591
references.citation: Proc Natl Acad Sci U S A. 1994 May 10;91(10):4407-11
references.pmid: 8183921
references.citation: Virology. 1993 May;194(1):50-8
references.pmid: 8386890
references.citation: Nature. 1981 Jul 30;292(5822):420-6
references.pmid: 7254339
references.citation: J Virol. 2006 Mar;80(6):3042-9
references.pmid: 16501113
references.citation: EMBO J. 1985 Mar;4(3):707-13
references.pmid: 3859409
references.citation: J Virol. 2006 Jul;80(14):6973-81
references.pmid: 16809303
references.citation: J Virol. 2009 Mar;83(6):2417-28
references.pmid: 19109384
references.citation: J Mol Biol. 1992 May 20;225(2):287-98
references.pmid: 1593621
references.citation: J Virol. 2009 Mar;83(6):2406-16
references.pmid: 19129452
references.citation: Gene. 2007 Mar 1;389(1):52-65
references.pmid: 17123746
references.citation: J Virol. 1991 Oct;65(10):5250-9
references.pmid: 1895382
references.citation: J Mol Biol. 1981 Jun 25;149(2):189-221
references.pmid: 6927849
references.citation: Virology. 1978 Oct 1;90(1):67-79
references.pmid: 716228
references.citation: J Virol. 1993 Jun;67(6):3226-31
references.pmid: 8497048
references.citation: J Virol. 2007 May;81(9):4744-52
references.pmid: 17301128
references.citation: J Gen Virol. 2003 Feb;84(Pt 2):259-268
references.pmid: 12560556
references.citation: Am J Epidemiol. 1969 Jan;89(1):25-50
references.pmid: 4303049
references.citation: Nature. 2002 Jul 18;418(6895):348-52
references.pmid: 12124628
references.citation: J Virol. 2009 Apr;83(7):3049-58
references.pmid: 19176628
references.citation: J Virol. 1981 Nov;40(2):585-93
references.pmid: 7321097
references.citation: J Virol. 1999 Mar;73(3):2253-62
references.pmid: 9971808
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17831-6
references.pmid: 15591107
references.citation: Mol Cell Biol. 1994 Jan;14(1):437-45
references.pmid: 8264611
references.citation: Proc Natl Acad Sci U S A. 1979 Aug;76(8):3665-9
references.pmid: 291030
references.citation: EMBO J. 1987 Jul;6(7):2045-52
references.pmid: 2820717
references.citation: J Virol. 1994 Jul;68(7):4450-7
references.pmid: 8207818
references.citation: Mol Cell Biol. 1986 Jan;6(1):201-8
references.pmid: 2946930
references.citation: J Virol. 1995 Nov;69(11):6627-33
references.pmid: 7474071
references.citation: J Virol. 1999 Feb;73(2):1591-600
references.pmid: 9882365