Neipel F, Albrecht J C, Ensser A, Huang Y Q, Li J J, Friedman-Kien A E, Fleckenstein B
Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Erlangen, Germany.
J Virol. 1997 Jan;71(1):839-42. doi: 10.1128/JVI.71.1.839-842.1997.
Kaposi's sarcoma is a multifocal lesion that is reported to be greatly influenced by cytokines such as interleukin-6 (IL-6) and oncostatin M. DNA sequences of a novel human gammaherpesvirus, termed human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus, have been identified in all epidemiological forms of Kaposi's sarcoma with high frequency. The presence of HHV-8 DNA is also clearly associated with certain B-cell lymphomas (body cavity-based lymphomas) and multicentric Castleman's disease. Sequence analysis of a 17-kb fragment revealed that adjacent to a block of conserved herpesvirus genes (major DNA-binding protein, glycoprotein B, and DNA polymerase), the genome of HHV-8 encodes structural homolog of IL-6. This cytokine is involved not only in the pathogenesis of Kaposi's sarcoma but also in certain B-cell lymphomas and multicentric Castleman's disease. The viral counterpart of IL-6 (vIL-6) has conserved important features such as cysteine residues involved in disulfide bridging or an amino-terminal signal peptide. Most notably, the region known to be involved in receptor binding is highly conserved in vIL-6. This conservation of essential features and the remarkable overlap between diseases associated with HHV-8 and diseases associated with IL-6 disregulation clearly suggest that vIL-6 is involved in HHV-8 pathogenesis.
卡波西肉瘤是一种多灶性病变,据报道它受细胞因子如白细胞介素-6(IL-6)和制瘤素M的影响很大。一种新型人类γ疱疹病毒,即人类疱疹病毒8(HHV-8)或卡波西肉瘤相关疱疹病毒的DNA序列,在所有流行病学形式的卡波西肉瘤中均被高频鉴定出。HHV-8 DNA的存在也与某些B细胞淋巴瘤(体腔淋巴瘤)和多中心性Castleman病明显相关。对一个17kb片段的序列分析表明,在一组保守的疱疹病毒基因(主要DNA结合蛋白、糖蛋白B和DNA聚合酶)旁边,HHV-8的基因组编码IL-6的结构同源物。这种细胞因子不仅参与卡波西肉瘤的发病机制,还参与某些B细胞淋巴瘤和多中心性Castleman病的发病机制。IL-6的病毒对应物(vIL-6)保留了重要特征,如参与二硫键桥接的半胱氨酸残基或氨基末端信号肽。最值得注意的是,已知参与受体结合的区域在vIL-6中高度保守。这些基本特征的保守性以及与HHV-8相关疾病和与IL-6失调相关疾病之间的显著重叠清楚地表明,vIL-6参与了HHV-8的发病机制。