E1A-CR3 interaction-dependent and -independent functions of mSur2 in viral replication of early region 1A mutants of mouse adenovirus type 1.
mSur2, a subunit of the Mediator complex, is required for efficient mouse adenovirus type 1 (MAV-1) replication (L. Fang, J. L. Stevens, A. J. Berk, and K. R. Spindler, J. Virol. 78:12888-12900, 2004). We examined the contributions of early-region 1A (E1A) to mSur2 function in MAV-1 replication with E1A mutant viruses. At a multiplicity of infection (MOI) of 1, viruses containing CR3 replicated better in Sur2+/+ mouse embryonic fibroblasts (MEFs) than in Sur2-/- MEFs. In contrast, viruses lacking CR3 replicated no better in Sur2+/+ than in Sur2-/- MEFs. This result supports the hypothesis that the E1A CR3-mSur2 interaction is important for MAV-1 replication. However, at an MOI of 0.05, viruses lacking CR3 showed replication defects in Sur2-/- MEFs compared to Sur2+/+ MEFs, suggesting an E1A CR3 interaction-independent function of mSur2 in MAV-1 replication in cell culture. Paradoxically, CR1Delta, CR2Delta, and CR3Delta mutant viruses replicated slightly more efficiently than wild-type (wt) MAV-1 and E1A null mutant viruses in Sur2-/- MEFs at an MOI of 0.05. Coinfection of Sur2-/- MEFs with wt MAV-1 and CR1Delta, CR2Delta, or CR3Delta mutant viruses rescued the defects of wt MAV-1 replication. This result suggests that an inhibiting effect on wt E1A protein expression and/or E1A function might account for the severe viral replication defect of MAV-1 in Sur2-/- MEFs at an MOI of 0.05. Moreover, titrations of virus yields from infected brains of inbred strains of mice showed that E1A null and CR3Delta mutant viruses had a significant defect in virus replication compared to wt MAV-1. This result supports the hypothesis that the MAV-1 E1A-mSur2 interaction is important in MAV-1 replication in mice.
Fang
Lei
L
Department of Microbiology and Immunology, University of Michigan Medical School, 1150 W. Medical Center Dr., 6723 Medical Science Bldg. II, Ann Arbor, MI 48109-0620, USA.
Spindler
Katherine R
KR
D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology*; D000257:Adenoviridae Infections; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000821:virology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000821:virology; D008297:Male; D051379:Mice; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D011955:Receptors, Drug; D017384:Sequence Deletion; D064233:Sulfonylurea Receptors; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
D018528:ATP-Binding Cassette Transporters; D017500:Adenovirus E1A Proteins; D004279:DNA, Viral; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D012367:RNA, Viral; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014764:Viral Proteins
J Virol. 2000 Mar;74(5):2084-93
10666238
J Virol. 2004 Dec;78(23):12888-900
15542641
J Virol. 2000 Jul;74(13):5819-24
10846061
Mol Cell Biol. 2000 Dec;20(23):8903-15
11073990
J Virol. 2001 Dec;75(24):12039-46
11711594
Science. 2002 Apr 26;296(5568):755-8
11934987
Cell. 2002 Jul 26;110(2):143-51
12150923
J Virol. 2002 Sep;76(18):9186-93
12186902
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12003-8
14506297
J Biol Chem. 2004 Jan 23;279(4):2666-72
14612439
Mol Cell. 2004 Jan 30;13(2):241-50
14759369
J Mol Biol. 1967 Jun 14;26(2):365-9
4291934
Nature. 1970 Aug 15;227(5259):680-5
5432063
Cold Spring Harb Symp Quant Biol. 1980;44 Pt 1,:367-75
6933036
Cell. 1981 Oct;26(2 Pt 2):213-20
7332929
Cell. 1983 Jul;33(3):683-93
6871990
Mol Cell Biol. 1984 May;4(5):867-74
6547205
Nature. 1984 Dec 13-19;312(5995):608-12
6095113
Cell. 1985 Mar;40(3):705-16
2982503
Science. 1985 Dec 20;230(4732):1391-4
2999984
Mol Cell Biol. 1987 Mar;7(3):1164-70
2951590
J Virol. 1990 Sep;64(9):4421-7
2143544
Virology. 1991 Jan;180(1):257-65
1845825
J Virol. 1992 Feb;66(2):1021-30
1309887
J Biol Chem. 1992 Dec 5;267(34):24886-91
1332971
J Virol. 1993 Jan;67(1):476-88
8416379
EMBO J. 1993 Feb;12(2):469-78
8440238
J Immunol. 1993 Apr 15;150(8 Pt 1):3602-14
8096853
Science. 1994 Jun 24;264(5167):1918-21
8009221
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10467-71
7479821
J Virol. 1995 Dec;69(12):7674-81
7494276
Virology. 1996 Oct 1;224(1):184-97
8862413
J Virol. 1998 Feb;72(2):1219-23
9445021
J Virol. 1998 Jul;72(7):5699-706
9621028
Virology. 1998 Jun 5;245(2):216-28
9636361
J Virol. 1998 Aug;72(8):6325-31
9658071
Nature. 1999 May 20;399(6733):276-9
10353252
J Virol. 2000 Apr;74(7):3366-78
10708454