Synergy between Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 and HIV-1 Nef protein in promotion of angiogenesis and oncogenesis: role of the AKT signaling pathway
Synergy between Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 and HIV-1 Nef protein in promotion of angiogenesis and oncogenesis: role of the AKT signaling pathway
复制标题
卡波西肉瘤相关疱疹病毒 (KSHV) vIL-6 和 HIV-1 Nef 蛋白在促进血管生成和肿瘤发生中的协同作用：AKT 信号通路的作用
作者：
Zhou, F.;Zhu, J.;Qin, D.;Lu, C.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma (KS), which is the most common AIDS-associated malignancy. KS is characterized by neovascularization and spindle cell proliferation. The interaction between HIV-1 and KSHV has a central role in promoting the aggressive manifestations of KS in AIDS patients; however, the pathogenesis underlying AIDS-related KS (AIDS–KS) remains unknown. Herein, we examined the potential of HIV-1 negative factor (Nef) to impact KSHV viral interleukin-6 (vIL-6)-induced angiogenesis and tumorigenesis. In vitro experiments showed that exogenous Nef penetrated vIL-6-expressing endothelial cells. Both internalized and ectopic expression of Nef in endothelial cells and fibroblasts synergized with vIL-6 to promote vascular tube formation and cell proliferation. Using a chicken chorioallantoic membrane (CAM) model, we demonstrated that Nef synergistically promotes vIL-6-induced angiogenesis and tumorigenesis. Animal experiments further showed that Nef facilitates vIL-6-induced angiogenesis and tumor formation in athymic nu/nu mice. Mechanistic studies indicated that Nef synergizes with vIL-6 to enhance angiogenesis and tumorigenesis by activating the AKT pathway in the CAM model, as well as nude mice. LY294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), significantly impaired the ability of Nef to promote vIL-6-induced tumorigenesis in an allograft model of nude mice. Our data provide first-line evidence that Nef may contribute to the pathogenesis underlying AIDS–KS in synergy with vIL-6. These novel findings also suggest that targeting the PI3K/AKT signal may be a potentially effective therapeutic approach in AIDS–KS patients.
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影响因子：
1.5
作者：
Raymond, A. D.;Campbell-Sims, T. C.;Powell, M. D.
通讯作者：
Powell, M. D.
影响因子：
3.8
作者：
S. Strathdee;P. Veugelers;P. Moore
通讯作者：
S. Strathdee;P. Veugelers;P. Moore
影响因子：
64.5
作者：
KESTLER, HW;RINGLER, DJ;DESROSIERS, RC
通讯作者：
DESROSIERS, RC
1 型单纯疱疹病毒诱导卡波西肉瘤相关疱疹病毒的裂解周期复制：IL-10 和 IL-4 的参与
影响因子：
3.4
作者：
Qin, Di;Zeng, Yi;Lu, Chun
通讯作者：
Lu, Chun
影响因子：
64.8
作者：
GUY, B;KIENY, MP;LECOCQ, JP
通讯作者：
LECOCQ, JP