Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid-lineage cells to induce inflammatory cytokine production.
Kaposi's sarcoma is an inflammatory cytokine-mediated angioproliferative disease which is triggered by infection by Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV contains an open reading frame, K14, that has significant homology with cellular OX2, designated viral OX2 (vOX2). In this report, we demonstrate that vOX2 encodes a glycosylated cell surface protein with an apparent molecular mass of 55 kDa. Purified glycosylated vOX2 protein dramatically stimulated primary monocytes, macrophages, and dendritic cells to produce the inflammatory cytokines interleukin 1beta (IL-1beta), IL-6, monocyte chemoattractant protein 1, and TNF-alpha. Furthermore, expression of vOX2 on B lymphocytes stimulated monocytes to produce inflammatory cytokines in mixed culture. These results demonstrate that like its cellular counterpart, vOX2 targets myeloid-lineage cells, but unlike cellular OX2, which delivers a restrictive signal, KSHV vOX2 provides an activating signal, resulting in the production of inflammatory cytokines. Thus, this is a novel viral strategy where KSHV has acquired the cellular OX2 gene to induce inflammatory cytokine production, which potentially promotes the cytokine-mediated angiogenic proliferation of KSHV-infected cells.
Chung
Young-Hwa
YH
Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
Means
Robert E
RE
Choi
Joong-Kook
JK
Lee
Bok-Soo
BS
Jung
Jae U
JU
D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000032:analysis / Q000096:biosynthesis; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D019084:Fluorescent Antibody Technique, Indirect; D006031:Glycosylation; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D022423:Myeloid Cells / Q000276:immunology / Q000821:virology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D018932:Chemokine CCL2; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins