Advanced

Characterization of the complement inhibitory function of Rhesus rhadinovirus complement control protein (RCP).

Okroj, Marcin LU ; Mark, Linda; Stokowska, Anna; Wong, Scott W; Rose, Nicola; Blackbourn, David J; Villoutreix, Bruno O; Spiller, O Brad and Blom, Anna LU (2009) In Journal of Biological Chemistry 2008(Nov 6.). p.505-514
Abstract
Rhesus Rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi's sarcoma-associated herpesvirus (KSHV). Both these viruses encode complement inhibitors: KSHV-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as complement inhibitor. Herein, we performed comparative analyses for two variants of RCP protein, encoded by RRV strains H26-95 and 17577. Both RCP variants and KCP inhibited human and rhesus complement when tested in hemolytic assays measuring all steps of activation via the classical and the alternative pathway. RCP variants from both RRV strains supported C3b- and C4b-degradation by factor I and... (More)
Rhesus Rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi's sarcoma-associated herpesvirus (KSHV). Both these viruses encode complement inhibitors: KSHV-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as complement inhibitor. Herein, we performed comparative analyses for two variants of RCP protein, encoded by RRV strains H26-95 and 17577. Both RCP variants and KCP inhibited human and rhesus complement when tested in hemolytic assays measuring all steps of activation via the classical and the alternative pathway. RCP variants from both RRV strains supported C3b- and C4b-degradation by factor I and decay-acceleration of the classical C3 convertase, similar to KCP. Additionally, the 17577 RCP variant accelerated decay of the alternative C3 convertase, which was not seen for KCP. In contrast to KCP, RCP showed no affinity to heparin and is the first described complement inhibitor in which the binding site for C3b/C4b does not interact with heparin. Molecular modeling shows a structural disruption in the region of RCP that corresponds to the KCP-heparin binding site. This makes RRV a superior model for future in vivo investigations of complement evasion, as RCP does not play a supportive role in viral attachment as KCP does. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
2008
issue
Nov 6.
pages
505 - 514
publisher
ASBMB
external identifiers
  • wos:000261974800055
  • pmid:18990693
  • scopus:58649105573
ISSN
1083-351X
DOI
10.1074/jbc.M806669200
language
English
LU publication?
yes
id
31fedfcc-9aeb-44d1-9718-f237df119ba1 (old id 1271730)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18990693?dopt=Abstract
date added to LUP
2008-12-01 16:52:57
date last changed
2017-07-02 03:45:33
@article{31fedfcc-9aeb-44d1-9718-f237df119ba1,
  abstract     = {Rhesus Rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi's sarcoma-associated herpesvirus (KSHV). Both these viruses encode complement inhibitors: KSHV-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as complement inhibitor. Herein, we performed comparative analyses for two variants of RCP protein, encoded by RRV strains H26-95 and 17577. Both RCP variants and KCP inhibited human and rhesus complement when tested in hemolytic assays measuring all steps of activation via the classical and the alternative pathway. RCP variants from both RRV strains supported C3b- and C4b-degradation by factor I and decay-acceleration of the classical C3 convertase, similar to KCP. Additionally, the 17577 RCP variant accelerated decay of the alternative C3 convertase, which was not seen for KCP. In contrast to KCP, RCP showed no affinity to heparin and is the first described complement inhibitor in which the binding site for C3b/C4b does not interact with heparin. Molecular modeling shows a structural disruption in the region of RCP that corresponds to the KCP-heparin binding site. This makes RRV a superior model for future in vivo investigations of complement evasion, as RCP does not play a supportive role in viral attachment as KCP does.},
  author       = {Okroj, Marcin and Mark, Linda and Stokowska, Anna and Wong, Scott W and Rose, Nicola and Blackbourn, David J and Villoutreix, Bruno O and Spiller, O Brad and Blom, Anna},
  issn         = {1083-351X},
  language     = {eng},
  number       = {Nov 6.},
  pages        = {505--514},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Characterization of the complement inhibitory function of Rhesus rhadinovirus complement control protein (RCP).},
  url          = {http://dx.doi.org/10.1074/jbc.M806669200},
  volume       = {2008},
  year         = {2009},
}