Autocrine CCL3 and CCL4 induced by the oncoprotein LMP1 promote epstein-barr virus-triggered B cell proliferation
Journal
Journal of Virology
Journal Volume
87
Journal Issue
16
Pages
9041-9052
Date Issued
2013
Author(s)
Tsai S.-C.
Lin S.-J.
Lin C.-J.
Chou Y.-C.
Lin J.-H.
Lu M.-Y.
Huang Y.-C.
Chen H.-Y.
Abstract
Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were de-tected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo. This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies. ? 2013, American Society for Microbiology.
SDGs
Other Subjects
cytokine antibody; latent membrane protein 1; macrophage inflammatory protein 1alpha; macrophage inflammatory protein 1beta; short hairpin RNA; stress activated protein kinase; adolescent; article; autocrine effect; B lymphocyte activation; cell growth; cell immortalization; cell survival; child; clinical article; controlled study; enzyme activation; Epstein Barr virus infection; female; human; human cell; immunocompromised patient; in vivo study; lymphoblastoid cell line; lymphocyte proliferation; male; preschool child; priority journal; protein domain; protein expression; protein function; school child; upregulation; B-Lymphocytes; Cell Proliferation; Chemokine CCL3; Chemokine CCL4; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; JNK Mitogen-Activated Protein Kinases; Signal Transduction; Viral Matrix Proteins
Type
journal article