KSHV-encoded CC chemokine vMIP-III is a CCR4 agonist, stimulates angiogenesis, and selectively chemoattracts TH2 cells

• Published in: Blood 2000-02, Vol.95 (4), p.1151-1157
• Main Authors: Stine, Johnny T., Wood, Christi, Hill, Mark, Epp, Angela, Raport, Carol J., Schweickart, Vicki L., Endo, Yoshio, Sasaki, Takuma, Simmons, Graham, Boshoff, Chris, Clapham, Paul, Chang, Yuan, Moore, Patrick, Gray, Patrick W., Chantry, David
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Allantois - blood supply; Animals; Biological and medical sciences; Cell Line; Chemokines, CC - genetics; Chemokines, CC - immunology; Chemokines, CC - pharmacology; Chemokines, CC - physiology; Chemotaxis - drug effects; Chemotaxis - physiology; Chick Embryo; CHO Cells; Chorion - blood supply; Cricetinae; Herpesvirus 8, Human - genetics; Herpesvirus 8, Human - immunology; HIV - drug effects; HIV - physiology; Human viral diseases; Humans; Infectious diseases; Medical sciences; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Open Reading Frames; Receptors, CCR4; Receptors, Chemokine - agonists; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Sarcoma, Kaposi - immunology; Sarcoma, Kaposi - pathology; Sarcoma, Kaposi - virology; Th1 Cells - drug effects; Th1 Cells - physiology; Th2 Cells - drug effects; Th2 Cells - physiology; Transfection; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Proteins; Virus Replication - drug effects
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V95.4.1151.004k37_1151_1157

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.