This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mark, L.
Right arrow Articles by Blackbourn, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mark, L.
Right arrow Articles by Blackbourn, D. J.

 Previous Article  |  Next Article 

Journal of Virology, April 2007, p. 4166-4176, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02069-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Molecular Characterization of the Rhesus Rhadinovirus (RRV) ORF4 Gene and the RRV Complement Control Protein It Encodes{triangledown}

Linda Mark,1 O. Brad Spiller,2 Marcin Okroj,1 Simon Chanas,3 Jim A. Aitken,4 Scott W. Wong,5 Blossom Damania,6 Anna M. Blom,1 and David J. Blackbourn3*

Department of Laboratory Medicine, Lund University, University Hospital Malmö, Malmö S-20502, Sweden,1 Department of Child Health, Cardiff University, Wales College of Medicine, Cardiff CF14 4XN, United Kingdom,2 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, United Kingdom,3 MRC Virology Unit, Church Street, Glasgow G11 5JR, United Kingdom,4 Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon 97006,5 Lineberger Comprehensive Cancer Center, University of North Carolina, CB 7295, Chapel Hill, North Carolina 275996

Received 21 September 2006/ Accepted 25 January 2007

The diversity of viral strategies to modulate complement activation indicates that this component of the immune system has significant antiviral potential. One example is the Kaposi's sarcoma-associated herpesvirus (KSHV) complement control protein (KCP), which inhibits progression of the complement cascade. Rhesus rhadinovirus (RRV), like KSHV, is a member of the subfamily Gammaherpesvirinae and currently provides the only in vivo model of KSHV pathobiology in primates. In the present study, we characterized the KCP homologue encoded by RRV, RRV complement control protein (RCP). Two strains of RRV have been sequenced to date (H26-95 and 17577), and the RCPs they encode differ substantially in structure: RCP from strain H26-95 has four complement control protein (CCP) domains, whereas RCP from strain 17577 has eight CCP domains. Transcriptional analyses of the RCP gene (ORF4, referred to herein as RCP) in infected rhesus macaque fibroblasts mapped the ends of the transcripts of both strains. They revealed that H26-95 encodes a full-length, unspliced RCP transcript, while 17577 RCP generates a full-length unspliced mRNA and two alternatively spliced transcripts. Western blotting confirmed that infected cells express RCP, and immune electron microscopy disclosed this protein on the surface of RRV virions. Functional studies of RCP encoded by both RRV strains revealed their ability to suppress complement activation by the classical (antibody-mediated) pathway. These data provide the foundation for studies into the biological significance of gammaherpesvirus complement regulatory proteins in a tractable, non-human primate model.

* Corresponding author. Mailing address: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TT, United Kingdom. Phone: 44 121 415 8804. Fax: 44 121 414 4486. E-mail: d.j.blackbourn{at}bham.ac.uk

{triangledown} Published ahead of print on 27 February 2007.

Journal of Virology, April 2007, p. 4166-4176, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02069-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wen, K. W., Dittmer, D. P., Damania, B. (2009). Disruption of LANA in Rhesus Rhadinovirus Generates a Highly Lytic Recombinant Virus. J. Virol. 83: 9786-9802 [Abstract] [Full Text]  
  • Wang, L., Pietrek, M., Brinkmann, M. M., Havemeier, A., Fischer, I., Hillenbrand, B., Dittrich-Breiholz, O., Kracht, M., Chanas, S., Blackbourn, D. J., Schulz, T. F. (2009). Identification and functional characterization of a spliced rhesus rhadinovirus gene with homology to the K15 gene of Kaposi's sarcoma-associated herpesvirus. J. Gen. Virol. 90: 1190-1201 [Abstract] [Full Text]  
  • Okroj, M., Mark, L., Stokowska, A., Wong, S. W., Rose, N., Blackbourn, D. J., Villoutreix, B. O., Spiller, O. B., Blom, A. M. (2009). Characterization of the Complement Inhibitory Function of Rhesus Rhadinovirus Complement Control Protein (RCP). J. Biol. Chem. 284: 505-514 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»