Rodent Herpesvirus Peru Encodes a Secreted Chemokine Decoy Receptor
Rodent Herpesvirus Peru Encodes a Secreted Chemokine Decoy Receptor
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DOI：
10.1128/jvi.02729-13
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发表时间：
2014-01-01
影响因子：
5.4
通讯作者：
Fremont, Daved H.
中科院分区：
文献类型：
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作者：
Lubman, Olga Y.;Cella, Marina;Fremont, Daved H.
长期以来，人们不仅对病毒的病理学和相关疾病进行了研究，而且将其作为理解细胞和免疫过程的模型系统。秘鲁啮齿动物疱疹病毒 (RHVP) 是一种最近鉴定的鼻病毒，与鼠伽马疱疹病毒 68 (MHV68) 和卡波西肉瘤相关疱疹病毒 (KSHV) 相关，可在实验室小鼠中引起急性和潜伏感染。 RHVP 编码许多独特的蛋白质，我们假设这些蛋白质可能有助于宿主在感染期间逃避免疫。我们在此报道开放阅读框 (ORF) R17 编码一种高亲和力趋化因子结合蛋白，可广泛识别人类和小鼠 CC 和 C 趋化因子。 R17与趋化因子的相互作用通常以快速缔合动力学为特征，对于CCL3、CCL4、CCL5、CCL24和XCL1，形成极其稳定的复合物。在功能上，R17 有效抑制 CCL2 驱动的人单核细胞系 THP-1 趋化性、CCL3 驱动的外周血单核细胞趋化性以及 CCL2 介导的钙流。我们的研究还表明，R17 在依赖于两个 BBXB 基序的过程中与糖胺聚糖 (GAG) 结合，并且趋化因子和 GAG 结合可以在不同位点同时发生。总的来说，这些研究表明，R17 可能通过有针对性地破坏趋化因子介导的免疫监视，在 RHVP 免疫逃避中发挥作用。
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. RHVP encodes numerous unique proteins that we hypothesize might facilitate host immune evasion during infection. We report here that open reading frame (ORF) R17 encodes a high-affinity chemokine binding protein that broadly recognizes human and murine CC and C chemokines. 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 and GAG binding can occur simultaneously at distinct sites. Collectively, these studies suggest that R17 may play a role in RHVP immune evasion through the targeted sabotage of chemokine-mediated immune surveillance.