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Functional activity of the complement regulator encoded by Kaposi's sarcoma associated herpesvirus.

Spiller, O. Brad; Blackbourn, David J.; Mark, Linda LU ; Proctor, David G. and Blom, Anna LU (2003) In Journal of Biological Chemistry 278(11). p.9283-9289
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is closely associated with Kaposi's sarcoma and certain B-cell lymphomas. The fourth open reading frame of the KSHV genome encodes a protein (KSHV complement control protein (KCP, previously termed ORF4)) predicted to have complement-regulating activity. Here, we show that soluble KCP strongly enhanced the decay of classical C3-convertase but not the alternative pathway C3-convertase, when compared with the host complement regulators: factor H, C4b-binding protein, and decay-accelerating factor. The equilibrium affinity constant (KD) of KCP for C3b and C4b was determined by surface plasmon resonance analysis to range between 0.47-10 µM and 0.025-6.1 µM, respectively, depending on NaCl... (More)
Kaposi's sarcoma-associated herpesvirus (KSHV) is closely associated with Kaposi's sarcoma and certain B-cell lymphomas. The fourth open reading frame of the KSHV genome encodes a protein (KSHV complement control protein (KCP, previously termed ORF4)) predicted to have complement-regulating activity. Here, we show that soluble KCP strongly enhanced the decay of classical C3-convertase but not the alternative pathway C3-convertase, when compared with the host complement regulators: factor H, C4b-binding protein, and decay-accelerating factor. The equilibrium affinity constant (KD) of KCP for C3b and C4b was determined by surface plasmon resonance analysis to range between 0.47-10 µM and 0.025-6.1 µM, respectively, depending on NaCl concentration and cation presence. Soluble and cell-associated KCP acted as a cofactor for factor I (FI)-mediated cleavage of both C4b and C3b and induced the cleavage products C4d and iC3b, respectively. In the presence of KCP, FI further cleaved iC3b to C3d, which has never been described before as complement receptor 1 only mediates the production of C3dg by FI. KCP would enhance virus pathogenesis through evading complement attack, opsonization, and anaphylaxis but may also aid in targeting KSHV to one of its host reservoirs since C3d is a ligand for complement receptor 2 on B-cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
278
issue
11
pages
9283 - 9289
publisher
ASBMB
external identifiers
  • wos:000181524000053
  • pmid:12645526
  • scopus:0037646403
ISSN
1083-351X
DOI
10.1074/jbc.M211579200
language
English
LU publication?
yes
id
c1fcadd3-3ea6-483a-a589-1b01ed74a050 (old id 112021)
date added to LUP
2007-07-27 09:15:13
date last changed
2018-10-14 03:40:12
@article{c1fcadd3-3ea6-483a-a589-1b01ed74a050,
  abstract     = {Kaposi's sarcoma-associated herpesvirus (KSHV) is closely associated with Kaposi's sarcoma and certain B-cell lymphomas. The fourth open reading frame of the KSHV genome encodes a protein (KSHV complement control protein (KCP, previously termed ORF4)) predicted to have complement-regulating activity. Here, we show that soluble KCP strongly enhanced the decay of classical C3-convertase but not the alternative pathway C3-convertase, when compared with the host complement regulators: factor H, C4b-binding protein, and decay-accelerating factor. The equilibrium affinity constant (KD) of KCP for C3b and C4b was determined by surface plasmon resonance analysis to range between 0.47-10 µM and 0.025-6.1 µM, respectively, depending on NaCl concentration and cation presence. Soluble and cell-associated KCP acted as a cofactor for factor I (FI)-mediated cleavage of both C4b and C3b and induced the cleavage products C4d and iC3b, respectively. In the presence of KCP, FI further cleaved iC3b to C3d, which has never been described before as complement receptor 1 only mediates the production of C3dg by FI. KCP would enhance virus pathogenesis through evading complement attack, opsonization, and anaphylaxis but may also aid in targeting KSHV to one of its host reservoirs since C3d is a ligand for complement receptor 2 on B-cells.},
  author       = {Spiller, O. Brad and Blackbourn, David J. and Mark, Linda and Proctor, David G. and Blom, Anna},
  issn         = {1083-351X},
  language     = {eng},
  number       = {11},
  pages        = {9283--9289},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Functional activity of the complement regulator encoded by Kaposi's sarcoma associated herpesvirus.},
  url          = {http://dx.doi.org/10.1074/jbc.M211579200},
  volume       = {278},
  year         = {2003},
}