Chou C S, Medveczky M M, Geck P, Vercelli D, Medveczky P G
Department of Medical Microbiology and Immunology, College of Medicine, University of South Florida, Tampa 33612-4799, USA.
Virology. 1995 Apr 20;208(2):418-26. doi: 10.1006/viro.1995.1172.
Herpesvirus saimiri (H. saimiri) is a highly oncogenic lymphotropic herpesvirus which can immortalize T lymphocytes and cause tumors in rabbits and New World monkeys. T cells infected with strain 484-77 of group C express four viral U-like small RNAs (HSUR1-4) and a 1.2-kb mRNA which encodes open reading frames ORF-1 and ORF-2. ORF-1 encodes a collagen-like oncoprotein. Deletion mutation analysis showed that ORF-1 and ORF-2 are essential for IL-2 independent growth of human T cells infected with H. saimiri. An earlier study also demonstrated that H. saimiri-immortalized cells carry functional IL-2 receptors. The work presented in this report investigated whether IL-2 and IL-4 is produced by H. saimiri-immortalized T lymphocytes. Both IL-2 mRNA and IL-4 mRNA were detected in various monkey T cells as well as human peripheral blood lymphocytes infected with wild-type H. saimiri. Secretion of IL-2 was suggested by cyclosporin A inhibition. IL-4 secretion by monkey T cell cultures was demonstrated by a bioassay and inhibition of bioactivity by an antibody to IL-4. The data also show that recombinant IL-4 stimulate H. saimiri-immortalized T cells; thus, IL-4 receptors are expressed. However, antibodies to human IL-4, IL-4 receptor, or soluble IL-4 receptor did not curtail growth of transformed cells. T cells infected with ORF-1 and ORF-2 deletion mutants expressed no detectable IL-2 mRNA. ORF-1, ORF-2, HSUR1, and HSUR2, were all essential for expression of IL-4 mRNA. These data are consistent with the hypothesis that H. saimiri-immortalized monkey and human T lymphocytes proliferate through autocrine secretion of IL-2 and that ORF-1, ORF-2, and HSUR sequences of the virus are involved in expression of lymphokines.
猴疱疹病毒（H. saimiri）是一种具有高度致癌性的嗜淋巴细胞疱疹病毒，可使T淋巴细胞永生化，并在兔和新大陆猴体内引发肿瘤。感染C组484 - 77株的T细胞表达四种病毒U样小RNA（HSUR1 - 4）和一种1.2 kb的mRNA，该mRNA编码开放阅读框ORF - 1和ORF - 2。ORF - 1编码一种胶原样癌蛋白。缺失突变分析表明，ORF - 1和ORF - 2对于感染H. saimiri的人T细胞在无白细胞介素 - 2（IL - 2）情况下的生长至关重要。一项早期研究还表明，H. saimiri永生化细胞携带功能性IL - 2受体。本报告中的研究调查了IL - 2和IL - 4是否由H. saimiri永生化的T淋巴细胞产生。在感染野生型H. saimiri的各种猴T细胞以及人外周血淋巴细胞中均检测到了IL - 2 mRNA和IL - 4 mRNA。环孢素A抑制表明有IL - 2的分泌。通过生物测定法证实了猴T细胞培养物中有IL - 4的分泌，并且抗IL - 4抗体抑制了其生物活性。数据还显示，重组IL - 4刺激H. saimiri永生化的T细胞；因此，表达了IL - 4受体。然而，抗人IL - 4、IL - 4受体或可溶性IL - 4受体的抗体并未抑制转化细胞的生长。感染ORF - 1和ORF - 2缺失突变体的T细胞未检测到可检测到的IL - 2 mRNA。ORF - 1、ORF - 2、HSUR1和HSUR2对于IL - 4 mRNA的表达均至关重要。这些数据与以下假设一致：H. saimiri永生化的猴和人T淋巴细胞通过IL - 2的自分泌分泌进行增殖，并且病毒的ORF - 1、ORF - 2和HSUR序列参与淋巴细胞因子的表达。
