Interaction of Epstein-Barr Virus Nuclear Antigen Leader Protein (EBNA-LP) with HS1-Associated Protein X-1: Implication of Cytoplasmic Function of EBNA-LP

doi:10.1128/JVI.74.21.10104-10111.2000

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Journal of Virology, November 2000, p. 10104-10111, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interaction of Epstein-Barr Virus Nuclear Antigen Leader Protein (EBNA-LP) with HS1-Associated Protein X-1: Implication of Cytoplasmic Function of EBNA-LP

Yasushi Kawaguchi, Kaori Nakajima, Mie Igarashi, Tomoko Morita, Michiko Tanaka, Mikiko Suzuki, Akihiko Yokoyama, Go Matsuda, Kentaro Kato, Mikiko Kanamori, and Kanji Hirai^*

Department of Tumor Virology, Division of Virology and Immunology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

Received 12 June 2000/Accepted 11 August 2000

Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) consists of W1W2 repeats and a unique C-terminal Y1Y2 domainand has been suggested to play an important role in EBV-inducedtransformation. To identify the cellular factors interacting withEBNA-LP, we performed a yeast two-hybrid screen, using EBNA-LPcDNA containing four W1W2 repeats as bait and an EBV-transformedhuman peripheral blood lymphocyte cDNA library as the source ofcellular genes. Our results were as follows. (i) All three cDNAsin positive yeast colonies were found to encode the same cellularprotein, HS1-associated protein X-1 (HAX-1), which is localizedmainly in the cytoplasm and has been suggested to be involvedin the regulation of B-cell signal transduction and apoptosis.(ii) Mutational analysis of EBNA-LP revealed that the associationwith HAX-1 is mediated by the W1W2 repeat domain. (iii) A purifiedchimeric protein consisting of glutathione S-transferase fusedto EBNA-LP specifically formed complexes with HAX-1 transientlyexpressed in COS-7 cells. (iv) When EBNA-LP and HAX-1 were coexpressedin COS-7 cells, EBNA-LP was specifically coimmunoprecipitatedwith HAX-1. (v) Careful cell fractionation experiments of an EBV-infectedlymphoblastoid cell line revealed that EBNA-LP is localized inthe cytoplasm as well as in the nucleus. (vi) When EBNA-LP containingfour W1W2 repeats was expressed in COS-7 cells, EBNA-LP was detectedmainly in the nucleus by immunofluorescence assay. Interestingly,when EBNA-LP containing a single W1W2 repeat was expressed inCOS-7 cells, EBNA-LP was localized predominantly in the cytoplasmand was colocalized with HAX-1. These results indicate that EBNA-LPis in fact present and may have a significant function in thecytoplasm, possibly by interacting with and affecting the functionof HAX-1.

^* Corresponding author. Mailing address: Department of Tumor Virology, Division of Virology and Immunology, Medical ResearchInstitute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku,Tokyo 113-8510, Japan. Phone: 81-3-5803-5815. Fax: 81-3-5803-0241.E-mail: hirai.creg{at}mri.tmd.ac.jp.

Journal of Virology, November 2000, p. 10104-10111, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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