Adenovirus late-phase infection is controlled by a novel L4 promoter.
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.
Morris
Susan J
SJ
Department of Biological Sciences, University of Warwick, Gibbet Hill Rd., Coventry CV4 7AL, United Kingdom.
Scott
Gillian E
GE
Leppard
Keith N
KN
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
D004279:DNA, Viral; D014764:Viral Proteins
J Cell Biol. 1995 Oct;131(1):45-56
7559785
J Virol. 2004 Feb;78(4):1782-91
14747543
Cell. 1978 Oct;15(2):497-510
719751
Virology. 1979 Apr 15;94(1):175-84
442530
J Biol Chem. 2006 Dec 1;281(48):36510-7
17028184
Virology. 1983 Jul 30;128(2):480-4
6310869
J Virol. 1996 Mar;70(3):1396-405
8627656
Genes Dev. 1996 Jan 15;10(2):196-207
8566753
J Virol. 2007 Apr;81(8):4264-71
17287283
J Thromb Haemost. 2006 Jun;4(6):1218-1225
16706963
J Biol Chem. 1992 Dec 15;267(35):25457-65
1460040
J Virol. 1996 Jul;70(7):4805-10
8676512
Cell. 1980 Dec;22(3):905-16
7460018
Cell. 1979 Aug;17(4):935-44
487437
Nucleic Acids Res. 1992 Aug 11;20(15):3881-9
1508674
J Virol. 2007 Feb;81(3):1327-38
17093188
J Gen Virol. 1999 Apr;80 ( Pt 4):997-1008
10211970
J Virol. 2008 Aug;82(15):7325-35
18480450
J Virol. 1989 Feb;63(2):631-8
2911117
Nature. 1981 Mar 12;290(5802):113-8
7207591
Proc Natl Acad Sci U S A. 1994 May 10;91(10):4407-11
8183921
Virology. 1993 May;194(1):50-8
8386890
Nature. 1981 Jul 30;292(5822):420-6
7254339
J Virol. 2006 Mar;80(6):3042-9
16501113
EMBO J. 1985 Mar;4(3):707-13
3859409
J Virol. 2006 Jul;80(14):6973-81
16809303
J Virol. 2009 Mar;83(6):2417-28
19109384
J Mol Biol. 1992 May 20;225(2):287-98
1593621
J Virol. 2009 Mar;83(6):2406-16
19129452
Gene. 2007 Mar 1;389(1):52-65
17123746
J Virol. 1991 Oct;65(10):5250-9
1895382
J Mol Biol. 1981 Jun 25;149(2):189-221
6927849
Virology. 1978 Oct 1;90(1):67-79
716228
J Virol. 1993 Jun;67(6):3226-31
8497048
J Virol. 2007 May;81(9):4744-52
17301128
J Gen Virol. 2003 Feb;84(Pt 2):259-268
12560556
Am J Epidemiol. 1969 Jan;89(1):25-50
4303049
Nature. 2002 Jul 18;418(6895):348-52
12124628
J Virol. 2009 Apr;83(7):3049-58
19176628
J Virol. 1981 Nov;40(2):585-93
7321097
J Virol. 1999 Mar;73(3):2253-62
9971808
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17831-6
15591107
Mol Cell Biol. 1994 Jan;14(1):437-45
8264611
Proc Natl Acad Sci U S A. 1979 Aug;76(8):3665-9
291030
EMBO J. 1987 Jul;6(7):2045-52
2820717
J Virol. 1994 Jul;68(7):4450-7
8207818
Mol Cell Biol. 1986 Jan;6(1):201-8
2946930
J Virol. 1995 Nov;69(11):6627-33
7474071
J Virol. 1999 Feb;73(2):1591-600
9882365