Tumorigenesis by human herpesvirus 8 vGPCR is accelerated by human immuodeficiency virus Type 1 Tat
Tumorigenesis by human herpesvirus 8 vGPCR is accelerated by human immuodeficiency virus Type 1 Tat
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DOI：
10.1128/jvi.78.17.9336-9342.2004
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发表时间：
2004-09-01
影响因子：
5.4
通讯作者：
Reitz, M
中科院分区：
文献类型：
--
作者：
Guo, HG;Pati, S;Reitz, M
人类疱疹病毒8（HHV-8），也称为卡波西肉瘤（KS）疱疹病毒，可以引起KS，但效率低下。未经治疗的人类免疫缺陷病毒1型（HIV-1）合并感染是一个强大的风险因素。HHV-8趋化因子受体vGPCR（ORF 74）激活NF-κ B和NF-AT，并且它们的激活水平通过HIV-1达特协同增加。转基因vGPCR小鼠产生KS样肿瘤来源于一种这样的肿瘤的细胞系表达vGPCR并在裸鼠中形成肿瘤。在这里，我们表明，将编码HIV-1达特（而不是反式激活缺陷突变体）的DNA转染到这些肿瘤细胞中，增加了NF-κ B和NF-AT的激活水平，并加速了肿瘤的形成。当达特DNA转染到正常细胞中，并将转染的细胞与肿瘤细胞混合并注射到单个部位时，肿瘤发生也被加速。当两种细胞类型在不同部位注射时，肿瘤发生也增加，表明肿瘤发生通过可溶性因子被达特加速。
Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma (KS) herpesvirus, can cause KS but is inefficient. Untreated human immunodeficiency virus type 1 (HIV-1) coinfection is a powerful risk factor. The HHV-8 chemokine receptor, vGPCR (ORF74), activates NF-kappaB and NF-AT, and their levels of activation are synergistically increased by HIV-1 Tat. Transgenic vGPCR mice develop KS-like tumors. A cell line derived from one such tumor expresses vGPCR and forms tumors in nude mice. Here we show that transfection of DNA encoding HIV-1 tat (but not a transactivation-defective mutant) into these tumor cells increases NF-kappaB and NF-AT activation levels and accelerates tumor formation. Tumorigenesis was also accelerated when Tat DNA was transfected into normal cells and the transfected cells were mixed with the tumor cells and injected into a single site. Tumorigenesis was also increased when the two cell types were injected at separate sites, suggesting that tumorigenesis is accelerated by Tat through soluble factors.