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Journal of Virology, July 1999, p. 6177-6181, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Rhesus Macaque Rhadinovirus Related to Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 Encodes a Functional Homologue of Interleukin-6

Johnan A. R. Kaleeba,1,2 Eric P. Bergquam,1 and Scott W. Wong1,2,*

Division of Pathobiology and Immunology,1 Oregon Regional Primate Research Center, Beaverton, Oregon 97006,1 and Department of Molecular Microbiology and Immunology,2 Oregon Health Sciences University, Portland, Oregon 97201

Received 8 February 1999/Accepted 12 April 1999

The rhesus rhadinovirus strain 17577 (RRV strain 17577) genome is essentially colinear with human herpesvirus 8 (HHV8)/Kaposi's sarcoma-associated herpesvirus (KSHV) and encodes several analogous open reading frames (ORFs), including the homologue of cellular interleukin-6 (IL-6). To determine if the RRV IL-6-like ORF (RvIL-6) is biologically functional, it was expressed either transiently in COS-1 cells or purified from bacteria as a glutathione S-transferase (GST)-RvIL-6 fusion and analyzed by IL-6 bioassays. Utilizing the IL-6-dependent B9 cell line, we found that both forms of RvIL-6 supported cell proliferation in a dose-dependent manner. Moreover, antibodies specific to the IL-6 receptor (IL-6R) or the gp130 subunit were capable of blocking the stimulatory effects of RvIL-6. Reciprocal titrations of GST-RvIL-6 against human recombinant IL-6 produced a more-than-additive stimulatory effect, suggesting that RvIL-6 does not inhibit but may instead potentiate normal cellular IL-6 signaling to B cells. These results demonstrate that RRV encodes an accessory protein with IL-6-like activity.

* Corresponding author. Mailing address: Oregon Regional Primate Research Center, Division of Pathobiology and Immunology, 505 N.W. 185th Ave., Beaverton, OR 97006. Phone: (503) 690-5534. Fax: (503) 690-5524. E-mail: wongs{at}ohsu.edu.

Journal of Virology, July 1999, p. 6177-6181, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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