title: E1A-CR3 interaction-dependent and -independent functions of mSur2 in viral replication of early region 1A mutants of mouse adenovirus type 1.
abstract: 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.
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Spindler
mesh_terms: 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
chemical_list: 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
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