SUBSTITUTE RAS FOR HERPESVIRUS SAIMIRI STP ONCOGENE IN LYMPHOCYTE TRANSFORMATION

STP-C488(C组疱疹病毒488株的STP [C488])是唯一与之相关的病毒编码蛋白 细胞ras和激活ras信号转导通路 探讨ras信号转导在细胞免疫中的重要作用 STP依赖的生长转化，我们构建了重组 其中STP-C488癌基因被替换的人类免疫缺陷病毒C488菌株 细胞内正常ras(c-ras)或病毒致癌ras(v-ras)重组 人类免疫缺陷病毒STP/v-ras永生化恒河猴原代T淋巴细胞 白细胞素-2独立生长与野生型HHS C488一样有效 (WT HVS)，而重组HVS STP/c-ras效率较低 而wt HVS使CD4-CD8+单阳性T淋巴细胞永生化， HVS STP/c-ras-和HVS STP/v-ras永生化细胞主要是 CD4+CD8+双阳性T淋巴细胞及人类免疫缺陷综合征 STP/v-ras永生化T细胞高水平表达ras 并表现出黏附的巨噬细胞样形态特征 可能是由于AP-1转录的剧烈激活所致 因子活性：HVS STP/v-ras和HVS STP/c-ras各自诱导 两种常见的绒猴中的一种发生淋巴瘤，尽管发病时间是 对于v-ras病毒，这些结果更快地表明ras可以 替代人类免疫缺陷病毒C488的STP癌基因，使其永生化 初级淋巴样细胞的生长和活化形式的ras 这样做比ras的正常细胞形式更有效。 出版物：郭，威廉姆斯，K，杜博伊斯，SM，亚历山大，L，韦兹，R. 和Jung，Ju用ras取代疱疹病毒saimiri stp 淋巴细胞转化中的癌基因J Virol 1998；72：3698-3704

STP-C488 (STP of herpesvirus saimiri [HVS] group C strain 488 [C488]) is the only virus-encoded protein found to associate with cellular ras and activate ras signal transduction pathways To investigate an important role for ras signal transduction in STP-dependent growth transformation, we constructed recombinant strains of HVS C488 in which the STP-C488 oncogene was replaced with cellular normal ras (c-ras) or viral oncogenic ras (v-ras) Recombinant HVS STP/v-ras immortalized primary common marmoset T lymphocytes to inter-leukin-2-independent growth as efficiently as wild-type HVS C488 (wt HVS), while recombinant HVS STP/c-ras did so with low efficiency Whereas wt HVS immortalized CD4- CD8+ single-positive T lymphocytes, HVS STP/c-ras- and HVS STP/v-ras-immortalized cells were principally CD4+ CD8+ double-positive T lymphocytes In addition, HVS STP/v-ras-immortalized T cells showed a high level of ras expression and exhibited an adherent macrophage-like morphol ogy These phenotypes were likely caused by the drastic activation of AP-1 transcriptional factor activity Finally, HVS STP/v-ras and HVS STP/c-ras each induced lymphoma in one of two common marmosets, although onset of disease was more rapid with the v-ras virus These results demonstrate that ras can substitute for the STP oncogene of HVS C488 to allow immortalized growth of primary lymphoid cells and that an activated form of ras does so more efficiently than the normal cellular form of ras PUBLICATIONS Guo, J, Williams, K, Duboise, SM, Alexander, L, Veazey, R and Jung, JU Substitution of ras for the herpesvirus saimiri STP oncogene in lymphocyte transformation J Virol 1998; 72:3698-3704