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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/112021
- author
- Spiller, O. Brad
; Blackbourn, David J.
; Mark, Linda
LU
; Proctor, David G.
and Blom, Anna
LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 278
- issue
- 11
- pages
- 9283 - 9289
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 12:38:17
- date last changed
- 2022-02-04 00:50:46
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M211579200}},
volume = {{278}},
year = {{2003}},
}