Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded vMIP-I and vMIP-II induce signal transduction and chemotaxis in monocytic cells.
Kaposi's sarcoma-associated herpesvirus (KSHV)/ Human herpesvirus 8 encodes three chemokines, which are called viral macrophage inflammatory protein (vMIP)-I, -II, and -III. Here, we expressed the KSHV vMIP-I and vMIP-II proteins and analyzed their biological functions. Both vMIP-I and vMIP-II had an apparent molecular mass of 7.8 kDa and were localized to the cytoplasm in a body cavity-based lymphoma cell line BC-3, stimulated with phorbol ester. We next treated a human monocytic leukemia cell line, THP-1, with purified recombinant vMIP-I and vMIP-II, or vMIP-I and vMIP-II fused with alkaline phosphatase to study Ca(2+) signalling and in vitro chemotaxis in response to these proteins. Calcium mobilization was induced by both vMIP-I and vMIP-II. Furthermore, vMIP-I and vMIP-II induced Ca(2+) mobilization in K562 cells expressing the CC chemokine receptor 5 (CCR5), suggesting that both may be agonistic for CCR5. Additionally, vMIP-I induced Ca(2+) mobilization through the intermediary of CCR8. These viral MIPs were also capable of chemotactically activating the THP-1 cells. These results imply that vMIP-I and vMIP-II may play important roles in the propagation of KS and primary effusion lymphoma by inducing the chemotaxis of CCR5-expressing monocytes.
Department of Microbiology C1, Osaka University Medical School, Japan.
K
K
Nakano
Y
Y
Isegawa
P
P
Zou
K
K
Tadagaki
R
R
Inagi
K
K
Yamanishi
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D054402:Chemokine CCL1; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D019742:Chemokines, CC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015846:Monokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
C065971:CCL1 protein, human; C515456:CCL11 protein, human; D054402:Chemokine CCL1; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019707:Receptors, Chemokine; D002118:Calcium