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Journal of Virology, April 2005, p. 4298-4307, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4298-4307.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Critical Role of Epstein-Barr Virus (EBV)-Encoded RNA in Efficient EBV-Induced B-Lymphocyte Growth Transformation

Misako Yajima,1,2 Teru Kanda,2 and Kenzo Takada1*

Department of Tumor Virology,1 Center for Virus Vector Development, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan2

Received 25 June 2004/ Accepted 5 November 2004

It was demonstrated that Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were nonessential for B-lymphocyte growth transformation. We revisited this issue by producing a large quantity of EBER-deleted EBV by using an Akata cell system. Although the EBER-deleted virus efficiently infected B lymphocytes, its 50% transforming dose was approximately 100-fold less than that of the EBER-positive EBV. We then engineered the genome of EBER-deleted virus and generated a recombinant virus with the EBER genes reconstituted at their native locus. The resultant EBER-reconstituted EBV exhibited restored transforming ability. In addition, lymphoblastoid cell lines established with the EBER-deleted EBV grew significantly more slowly than those established with wild-type or EBER-reconstituted EBV, and the difference between the growth rates was especially highlighted when the cells were plated at low cell densities. These results clearly demonstrate that EBERs significantly contribute to the efficient growth transformation of B lymphocytes by enhancing the growth potential of transformed lymphocytes.


* Corresponding author. Mailing address: Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University N15 W7, Kita-ku, Sapporo 060-0815, Japan. Phone: 81-11-706-5071. Fax: 81-11-706-7540. E-mail: kentaka{at}igm.hokudai.ac.jp.


Journal of Virology, April 2005, p. 4298-4307, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4298-4307.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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