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Journal of Virology, April 2005, p. 4651-4663, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4651-4663.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Activation of CD21 and CD23 Gene Expression by Kaposi's Sarcoma-Associated Herpesvirus RTA

Heesoon Chang,1 Yousang Gwack,1 Dior Kingston,1 John Souvlis,1 Xiaozhen Liang,1 Robert E. Means,1 Ethel Cesarman,2 Lindsey Hutt-Fletcher,3 and Jae U. Jung1*

Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts,1 Department of Pathology, Weil Medical College, Cornell University, New York, New York,2 Department of Microbiology and Immunology, Louisiana State University Health Science Center, Shreveport, Louisiana3

Received 13 August 2004/ Accepted 23 November 2004

Epstein-Barr virus (EBV) EBNA2 and Kaposi's sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) are recruited to their responsive elements through interaction with a Notch-mediated transcription factor, RBP-J{kappa}. In particular, RTA and EBNA2 interactions with RBP-J{kappa} are essential for the lytic replication of KSHV and expression of B-cell activation markers CD21 and CD23a, respectively. Here, we demonstrate that like EBV EBNA2, KSHV RTA strongly induces CD21 and CD23a expression through RBP-J{kappa} binding sites in the first intron of CD21 and in the CD23a core promoter, respectively. However, unlike EBV EBNA2, which alters immunoglobulin µ (Igµ) and c-myc gene expression, RTA did not affect Igµ and c-myc expression, indicating that KSHV RTA targets the Notch signal transduction pathway in a manner similar to but distinct from that of EBV EBNA2. Furthermore, RTA-induced expression of CD21 glycoprotein, which is an EBV receptor, efficiently facilitated EBV infection. In addition, RTA-induced CD23 glycoprotein underwent proteolysis and gave rise to soluble CD23 (sCD23) molecules in B lymphocytes and KSHV-infected primary effusion lymphocytes. sCD23 then stimulated primary human lymphocytes. These results demonstrate that cellular CD21 and CD23a are common targets for B lymphotropic gammaherpesviruses and that KSHV RTA regulates RBP-J{kappa}-mediated cellular gene expression, which ultimately provides a favorable milieu for viral reproduction in the infected host.

* Corresponding author. Mailing address: Tumor Virology Division, New England Primate Research Center, Harvard Medical School, 1 Pine Hill Dr., Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508) 786-1416. E-mail: jae_jung{at}hms.harvard.edu.

Journal of Virology, April 2005, p. 4651-4663, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4651-4663.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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