title: Requirement of Sur2 for efficient replication of mouse adenovirus type 1.
abstract: Mouse adenovirus type 1 (MAV-1) early region 1A (E1A) encodes a virulence gene in viral infection of mice. To broaden our understanding of the functions of E1A in MAV-1 pathogenesis, an unbiased experimental approach, glutathione S-transferase (GST) pulldown, was used to screen for cellular proteins that interact with E1A protein. We identified mouse Sur2, a subunit of Mediator complex, as a protein that binds to MAV-1 E1A. The interaction between Sur2 and MAV-1 E1A was confirmed in virus-infected cells. Conserved region 3 (CR3) of MAV-1 E1A was mapped as the region required for Sur2-E1A interaction, as is the case for human adenovirus E1A. Although it has been proposed that human adenovirus E1A recruits the Mediator complex to transactivate transcription of viral early genes, Sur2 function in adenovirus replication has not been directly tested previously. Studies on the functions of Sur2 with mouse embryonic fibroblasts (MEFs) showed that there was a multiplicity-dependent growth defect of MAV-1 in Sur2(-/-) MEFs compared to Sur2(+/+) MEFs. Comparison of the viral DNA and viral mRNA levels in Sur2(+/+) and Sur2(-/-) MEFs confirmed that Sur2 was important for efficient viral replication. The viral replication defects in Sur2(-/-) MEFs appeared to be due at least in part to a defect in viral early gene transcription.
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. krspin@umich.edu
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Jennitte L
authors.initials: JL
authors.lastname: Stevens
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Berk
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Spindler
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000256:Adenoviridae / Q000502:physiology*; D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014779:Virus Replication
chemical_list: C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; D017500:Adenovirus E1A Proteins; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors