Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6
Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6
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DOI：
10.1038/nm0397-287
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发表时间：
1997-03-01
期刊：
影响因子：
82.9
通讯作者：
Reitz, MS
中科院分区：
文献类型：
--
作者：
Nicholas, J;Ruvolo, VR;Reitz, MS
人类疱疹病毒 8 (HHV-8) 已在所有类型的卡波西肉瘤 (KS) 病变（艾滋病相关的、经典的和地方性的）、体腔 B 细胞淋巴瘤 (BCBL) 和多中心卡斯尔曼病 (MCD) 的病变中检测到。我们在 HHV-8 DNA 中鉴定出一个主要的 γ-疱疹病毒分歧位点 (DL-B)，编码多个 HHV-8 独特的开放阅读框 (ORF)，包括白介素 6 (IL-6) 同源物和巨噬细胞炎症蛋白 MIP-1 的两个同源物。我们发现，HHV-8 编码的 IL-6 同源物 (vIL-6) 与内源性 IL-6 蛋白具有相同的功能特性，并且在丁酸盐诱导 HHV-8(+) BCBL 细胞系后，vIL-6 和 vMIP-1 转录物均以高水平存在。还检测到少量的组成型 vIL-6，但未检测到 vMIP-1 mRNA。 HHV-8 编码的功能性 IL-6 同源物的存在可能为 HHV-8 在 KS、MCD 和 BCBL 中的假设作用提供了机制模型，其中涉及 vIL-6 对周围细胞的有丝分裂作用。 MIP-1 蛋白可能通过将内源性细胞因子产生细胞趋化募集到受影响的组织中来增强这些作用，并可能通过与 HIV 共受体 CCR-5 的相互作用影响共感染个体的 HIV 疾病进展。
Human herpesvirus-8 (HHV-8) has been detected in Kaposi's sarcoma (KS) lesions of all types (AIDS-related, classical and endemic), in body-cavity-based B-cell lymphomas (BCBLs) and in lesions of multicentric Castleman's disease (MCD). We have identified a major gamma-herpesvirus-divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1. We show that the HHV-8-encoded IL-6 homologue (vIL-6) shares functional properties with endogenous IL-6 proteins and that both vIL-6 and vMIP-1 transcripts are present at high levels following butyrate induction of an HHV-8(+) BCBL cell line. Low amounts of constitutive vIL-6, but not vMIP-1, mRNA were also detected. The presence of a functional IL-6 homologue encoded by HHV-8 may provide a mechanistic model for the hypothesized role of HHV-8 in KS, MCD and BCBL that involves the mitogenic effects of vIL-6 on surrounding cells. MIP-1 proteins may enhance these effects through the chemotactic recruitment of endogenous cytokine-producing cells into affected tissues and could potentially influence HIV disease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5.