Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded vMIP-I and vMIP-II induce signal transduction and chemotaxis in monocytic cells.

Abstract

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.

• Authors: K Nakano, Y Isegawa, P Zou, K Tadagaki, R Inagi, K Yamanishi
• Journal: Archives of virology (Arch Virol) Vol. 148 Issue 5 Pg. 871-90 (May 2003) ISSN: 0304-8608 [Print] Austria
• PMID: 12721796 (Publication Type: Journal Article)

Chemical References

• CCL1 protein, human
• CCL11 protein, human
• Chemokine CCL1
• Chemokine CCL11
• Chemokine CCL4
• Chemokine CXCL2
• Chemokines, CC
• Macrophage Inflammatory Proteins
• Monokines
• Receptors, Chemokine
• Calcium

Topics

• Calcium (metabolism)
• Calcium Signaling (drug effects)
• Chemokine CCL1
• Chemokine CCL11
• Chemokine CCL4
• Chemokine CXCL2
• Chemokines, CC (pharmacology)
• Chemotaxis (drug effects)
• Dose-Response Relationship, Drug
• Gene Expression
• Herpesvirus 8, Human (physiology)
• Humans
• K562 Cells
• Macrophage Inflammatory Proteins (genetics, metabolism, pharmacology)
• Monocytes (cytology, drug effects, metabolism)
• Monokines (genetics, metabolism, pharmacology)
• Receptors, Chemokine (genetics, metabolism)
• Sarcoma, Kaposi (virology)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured