KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells.
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 3 genes that are homologous to cellular chemokines. vMIP-III, the product of open reading frame K4.1, is the most distantly related to human chemokines and has yet to be characterized. We have examined the interaction of vMIP-III with chemokine receptors, its expression in KS lesions, and its in ovo angiogenic properties. We show expression of vMIP-III in KS lesions and demonstrate the stimulation of angiogenesis by this chemokine, like vMIP-I and vMIP-II, in the chick chorioallantoic membrane assay. vMIP-III does not block human immunodeficiency virus entry through the coreceptors CCR3, CCR5, or CXCR4. However, vMIP-III is an agonist for the cellular chemokine receptor CCR4. CCR4 is expressed by TH2-type T cells. Consistent with this, vMIP-III preferentially chemoattracts this cell type. Because of these biologic properties and because it is expressed in KS lesions, vMIP-III may play an important role in the pathobiology of KS. (Blood. 2000;95:1151-1157)
Stine
J T
JT
ICOS Corporation, Bothell, WA 98021, USA.
Wood
C
C
Hill
M
M
Epp
A
A
Raport
C J
CJ
Schweickart
V L
VL
Endo
Y
Y
Sasaki
T
T
Simmons
G
G
Boshoff
C
C
Clapham
P
P
Chang
Y
Y
Moore
P
P
Gray
P W
PW
Chantry
D
D
D000482:Allantois / Q000098:blood supply; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D019742:Chemokines, CC / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D006224:Cricetinae; D006678:HIV / Q000187:drug effects / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D016366:Open Reading Frames; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000819:agonists*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000276:immunology / Q000473:pathology / Q000821:virology; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology; D018418:Th2 Cells / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014764:Viral Proteins; D014779:Virus Replication / Q000187:drug effects
C515354:CCR4 protein, human; D019742:Chemokines, CC; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D014764:Viral Proteins; C404961:vMIP-III protein, Herpesvirus 8, Human