McNees Adrienne L, Vilchez Regis A, Heard Tiffany C, Sroller Vojtech, Wong Connie, Herron Alan J, Hamilton Mary J, Davis William C, Butel Janet S
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Virology. 2009 Feb 5;384(1):114-24. doi: 10.1016/j.virol.2008.10.035. Epub 2008 Nov 28.
Simian virus 40 (SV40) isolates differ in oncogenic potential in Syrian golden hamsters following intraperitoneal inoculation. Here we describe the effect of intravenous exposure on tumor induction by SV40. Strains SVCPC (simple regulatory region) and VA45-54(2E) (complex regulatory region) were highly oncogenic following intravenous inoculation, producing a spectrum of tumor types. Three lymphoma cell lines were established; all expressed SV40 T-antigen, were immortalized for growth in culture, and were tumorigenic following transplantation in vivo. New monoclonal antibodies directed against hamster lymphocyte surface antigens are described. The cell lines expressed MHC class II and macrophage markers and were highly phagocytic, indicating a histiocytic origin. Many hamsters that remained tumor-free developed SV40 T-antigen antibodies, suggesting that viral replication occurred. This study shows that route of exposure influences the pathogenesis of SV40-mediated carcinogenesis, that SV40 strain VA45-54(2E) is lymphomagenic in hamsters, that hamster lymphoid cells of histiocytic origin can be transformed in vivo and established in culture, and that reagents to hamster leukocyte differentiation molecules are now available.
在叙利亚金黄地鼠腹腔内接种后,猿猴病毒40(SV40)分离株在致癌潜力方面存在差异。在此,我们描述静脉暴露对SV40诱导肿瘤的影响。SVCPC(简单调控区)和VA45 - 54(2E)(复杂调控区)毒株在静脉接种后具有高度致癌性,可产生一系列肿瘤类型。建立了三种淋巴瘤细胞系;所有细胞系均表达SV40 T抗原,在培养中可永生化生长,且在体内移植后具有致瘤性。描述了针对仓鼠淋巴细胞表面抗原的新型单克隆抗体。这些细胞系表达MHC II类分子和巨噬细胞标志物,且具有高度吞噬作用,表明其起源于组织细胞。许多未发生肿瘤的仓鼠产生了SV40 T抗原抗体,提示发生了病毒复制。本研究表明,暴露途径会影响SV40介导的致癌作用的发病机制,SV40毒株VA45 - 54(2E)在仓鼠中具有致淋巴瘤性,起源于组织细胞的仓鼠淋巴细胞可在体内转化并在培养中建立,且现在已有针对仓鼠白细胞分化分子的试剂。