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Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1151-1157
KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates
angiogenesis, and selectively chemoattracts TH2 cells
Johnny T. Stine,
Christi Wood,
Mark Hill,
Angela Epp,
Carol J. Raport,
Vicki L. Schweickart,
Yoshio Endo,
Takuma Sasaki,
Graham Simmons,
Chris Boshoff,
Paul Clapham,
Yuan Chang,
Patrick Moore,
Patrick W. Gray, and
David Chantry
From ICOS Corporation, Bothell, WA; Cancer Research Institute,
Kanazawa University, Kanazawa, Japan; University College Hospital,
London, UK; and the Department of Pathology and Epidemiology, College
of Physicians and Surgeons of Columbia University, New York,
NY.
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.
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