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Journal of Virology, March 2005, p. 3267-3276, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3267-3276.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

E1A-CR3 Interaction-Dependent and -Independent Functions of mSur2 in Viral Replication of Early Region 1A Mutants of Mouse Adenovirus Type 1

Lei Fang^1, and Katherine R. Spindler^2*

Department of Genetics, Franklin College of Arts and Sciences, University of Georgia, Athens, Georgia,¹ Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan²

Received 18 August 2004/ Accepted 23 November 2004

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, CR1, CR2, and CR3 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 CR1, CR2, or CR3 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 CR3 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.

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* Corresponding author. Mailing address: 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. Phone: (734) 615-3531. Fax: (734) 764-3562. E-mail: krspin{at}umich.edu.

Present address: Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, Calif.

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Journal of Virology, March 2005, p. 3267-3276, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3267-3276.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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