Rodent herpesvirus Peru encodes a secreted chemokine decoy receptor

Olga Y. Lubman, Marina Cella, Xinxin Wang, Kristen Monte, Deborah J. Lenschow, Yina H. Huang, Daved H. Fremont

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Viruses have long been studied not only for their pathology and associated disease but also as model systems for understanding cellular and immunological processes. Rodent herpesvirus Peru (RHVP) is a recently characterized rhadinovirus related to murine gammaherpesvirus 68 (MHV68) and Kaposi's sarcoma-associated herpesvirus (KSHV) that establishes acute and latent infection in laboratory mice.RHVPencodes numerous unique proteins that we hypothesize might facilitate host immune evasion during infection.Wereport here that open reading frame (ORF) R17 encodes a high-affinity chemokine binding protein that broadly recognizes human and murineCCandCchemokines. The interaction of R17 with chemokines is generally characterized by rapid association kinetics, and in the case of CCL3, CCL4, CCL5, CCL24, and XCL1, extremely stable complexes are formed. Functionally, R17 potently inhibited CCL2-driven chemotaxis of the human monocytic cell line THP-1, CCL3-driven chemotaxis of peripheral blood mononuclear cells, and CCL2-mediated calcium flux. Our studies also reveal that R17 binds to glycosaminoglycans (GAGs) in a process dependent upon two BBXB motifs and that chemokine andGAGbinding can occur simultaneously at distinct sites. Collectively, these studies suggest that R17 may play a role inRHVPimmune evasion through the targeted sabotage of chemokine-mediated immune surveillance.

Original languageEnglish
Pages (from-to)538-546
Number of pages9
JournalJournal of virology
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2014

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