Envelope-induced cell transformation by ovine betaretroviruses
Envelope-induced cell transformation by ovine betaretroviruses
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DOI：
10.1128/jvi.76.11.5387-5394.2002
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发表时间：
2002-06-01
影响因子：
5.4
通讯作者：
Palmarini, M
中科院分区：
文献类型：
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作者：
Alberti, A;Murgia, C;Palmarini, M
绵羊β逆转录病毒包括Jaagsiekte羊逆转录病毒(JSRV)和地方性鼻肿瘤病毒(ENTV)。 JSRV 和 ENTV 代表一类独特的致癌逆转录病毒，可诱发呼吸道肿瘤。 JSRV 和 ENTV 高度相关，但诱发不同的疾病。 JSRV 包膜 (Env) 的表达诱导啮齿动物成纤维细胞体外转化和 Akt 磷酸化，Akt 是磷脂酰肌醇 3-激酶 (PI-3K)/Akt 信号转导途径的核心参与者。然而，关于 ENTV 分子生物学的信息很少。在本研究中，我们初步评估了 ENTV Env 是否具有与同源 JSRV 蛋白相同的特性。我们使用用 JSRV 或 ENTV Env 假型化的逆转录病毒载体和绵羊脉络丛细胞、稳定表达 JSRV Env 蛋白的脉络丛细胞、人 293T 细胞、小鼠 NIH 3T3 细胞或表达人透明质酸酶 2 (HYAL2)（JSRV 的细胞受体）的 NIH 3T3 细胞进行进入和干扰测定。获得的结果表明ENTV和JSRV在绵羊细胞中具有相同的受体，并且它们可以使用人HYAL2作为小鼠细胞中的细胞受体。 ENTV Env 在体外诱导啮齿动物成纤维细胞的转化。与 JSRV Env 一样，590 位的酪氨酸对于 ENTV Env 诱导的细胞转化至关重要，Akt 在 ENTV Env 转化的细胞中被磷酸化，但在亲本细胞系中则不然。因此，绵羊β逆转录病毒具有共同的细胞转化机制。我们进一步研究了绵羊β逆转录病毒转化的细胞中 Akt 激活的相关性。 PI-3K 抑制剂可阻断 JSRV Env 转化细胞中的 Akt 磷酸化，表明 PI-3K 可能参与 JSRV 和 ENTV Env 诱导的细胞转化。此外，在源自患有天然绵羊肺腺癌的绵羊肺肿瘤的细胞系中检测到磷酸化 Akt。
Ovine betaretroviruses include Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV). JSRV and ENTV represent a unique class of oncogenic retroviruses that induce tumors of the respiratory tract. JSRV and ENTV are highly related but induce different diseases. Expression of the JSRV envelope (Env) induces transformation of rodent fibroblasts in vitro and phosphorylation of Akt, a central player in the phosphatidylinositol 3-kinase (PI-3K)/Akt signal transduction pathway. However, little information is available on the molecular biology of ENTV. In this study, we initially assessed whether the ENTV Env has the same properties as the homologous JSRV protein. We performed entry and interference assays using retroviral vectors pseudotyped with either the JSRV or the ENTV Env and sheep choroid plexus cells, choroid plexus cells stably expressing the JSRV Env protein, human 293T cells, mouse NIH 3T3 cells, or NIH 3T3 cells expressing human hyaluronidase 2 (HYAL2), the cellular receptor for JSRV. The results obtained indicated that ENTV and JSRV share the same receptor in sheep cells and that they can use human HYAL2 as a cellular receptor in mouse cells. The ENTV Env induces transformation of rodent fibroblasts in vitro. As with the JSRV Env, the tyrosine at position 590 is critical for ENTV Env-induced cell transformation, and Akt is phosphorylated in ENTV Env-transformed cells but not in the parental cell lines. Thus, ovine betaretroviruses share a common mechanism of cell transformation. We further investigated the relevance of Akt activation in cells transformed by ovine betaretroviruses. A PI-3K inhibitor blocked Akt phosphorylation in JSRV Env-transformed cells, suggesting a possible involvement of PI-3K in JSRV and ENTV Env-induced cell transformation. In addition, phosphorylated Akt was detected in a cell line derived from a lung tumor of a sheep with naturally occurring ovine pulmonary adenocarcinoma.