A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus

被引:400
作者
Kledal, TN
Rosenkilde, MM
Coulin, F
Simmons, G
Johnsen, AH
Alouani, S
Power, CA
Luttichau, HR
Gerstoft, J
Clapham, PR
ClarkLewis, I
Wells, TNC
Schwartz, TW
机构
[1] GLAXO WELLCOME RES & DEV LTD,GENEVA BIOMED RES INST,CH-1228 PLAN LES OUATES,GENEVA,SWITZERLAND
[2] UNIV COPENHAGEN,PANUM INST,MOL PHARMACOL LAB,INST PHARMACOL,DK-2200 COPENHAGEN,DENMARK
[3] RIGSHOSP,DEPT INFECT DIS,DK-2100 COPENHAGEN,DENMARK
[4] INST CANC RES,CHESTER BEATTY LABS,SECT VIROL,LONDON SW3 6JB,ENGLAND
[5] UNIV BRITISH COLUMBIA,BIOMED RES CTR,VANCOUVER,BC V6T 1Z3,CANADA
关键词
D O I
10.1126/science.277.5332.1656
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II, This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a number of both CC and CXC chemokine receptors, Binding of vMIP-II, however, was not associated with the normal, rapid mobilization of calcium from intracellular stores; instead, it blocked calcium mobilization induced by endogenous chemokines, In freshly isolated human monocytes the virally encoded vMIP-II acted as a potent and efficient antagonist of chemotaxis induced by chemokines. Because vMIP-II could inhibit cell entry of human immunodeficiency virus (HIV) mediated through CCR3 and CCR5 as well as CXCR4, this protein may serve as a lead for development of broad-spectrum anti-HIV agents.
引用
收藏
页码:1656 / 1659
页数:4
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