A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus.
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.
Kledal
T N
TN
Laboratory for Molecular Pharmacology, Institute of Pharmacology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Rosenkilde
M M
MM
Coulin
F
F
Simmons
G
G
Johnsen
A H
AH
Alouani
S
S
Power
C A
CA
Lüttichau
H R
HR
Gerstoft
J
J
Clapham
P R
PR
Clark-Lewis
I
I
Wells
T N
TN
Schwartz
T W
TW
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D015497:HIV-1 / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
D018946:Chemokine CCL5; D018925:Chemokines; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D011994:Recombinant Proteins; C108059:vMIP-II; D002118:Calcium