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Journal of Virology, July 2008, p. 6395-6408, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00043-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

RUNX1 Permits E4orf6-Directed Nuclear Localization of the Adenovirus E1B-55K Protein and Associates with Centers of Viral DNA and RNA Synthesis{triangledown}

Leslie J. Marshall,1,{dagger} Amy C. Moore,2,{dagger} Misao Ohki,3 Issay Kitabayashi,3 David Patterson,4 and David A. Ornelles1*

Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157,1 Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,2 Molecular Oncology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan,3 Eleanor Roosevelt Institute, Department of Biological Sciences, University of Denver, 2101 E. Wesley Ave., Denver, Colorado 802084

Received 7 January 2008/ Accepted 9 April 2008

The localization of the adenovirus E1B-55K-E4orf6 protein complex is critical for its function. Prior studies demonstrated that E4orf6 directs the nuclear localization of E1B-55K in human cells and in rodent cells that contain part of human chromosome 21. We show here that the relevant activity on chromosome 21 maps to RUNX1. RUNX1 proteins are transcription factors that serve as scaffolds for the assembly of proteins that regulate transcription and RNA processing. After transfection, the RUNX1a, RUNX1b, and RUNX1-{Delta}N variants allowed E4orf6-directed E1B-55K nuclear localization. The failure of RUNX1c to allow nuclear colocalization was relieved by the deletion of amino-terminal residues of this protein. In the adenovirus-infected mouse cell, RUNX1 proteins were localized to discrete structures about the periphery of viral replication centers. These sites are enriched in viral RNA and RNA-processing factors. RUNX1b and RUNX1a proteins displaced E4orf6 from these sites. The association of E1B-55K at viral replication centers was enhanced by the RUNX1a and RUNX1b proteins, but only in the absence of E4orf6. In the presence of E4orf6, E1B-55K occurred in a perinuclear cytoplasmic body resembling the aggresome and was excluded from the nucleus of the infected mouse cell. We interpret these findings to mean that a dynamic relationship exists between the E4orf6, E1B-55K, and RUNX1 proteins. In cooperation with E4orf6, RUNX1 proteins are able to modulate the localization of E1B-55K and even remodel virus-specific structures that form at late times of infection. Subsequent studies will need to determine a functional consequence of the interaction between E4orf6, E1B-55K, and RUNX1.

* Corresponding author. Mailing address: Medical Center Blvd., Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157. Phone: (336) 716-9332. Fax: (336) 716-9928. E-mail: ornelles{at}wfubmc.edu

{triangledown} Published ahead of print on 16 April 2008.

{dagger} L.J.M. and A.C.M. contributed equally to this work.

Journal of Virology, July 2008, p. 6395-6408, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00043-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Blackford, A. N., Grand, R. J. A. (2009). Adenovirus E1B 55-Kilodalton Protein: Multiple Roles in Viral Infection and Cell Transformation. J. Virol. 83: 4000-4012 [Full Text]  


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