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2只自然感染狒狒中的猿猴嗜T淋巴细胞病毒相关淋巴瘤:肿瘤发生过程中的T细胞克隆性扩增及免疫反应

Simian T-lymphotropic Virus-associated lymphoma in 2 naturally infected baboons: T-cell clonal expansion and immune response during tumor development.

作者信息

d'Offay Jean M, Eberle Richard, Wolf Roman F, Kosanke Stanley D, Doocy Kelly R, Ayalew Sahlu, Mansfeild Keith G, White Gary L

机构信息

Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.

出版信息

Comp Med. 2013 Jun;63(3):288-94.

Abstract

Two young female baboons naturally infected with simian T-lymphotropic virus type 1 (STLV1) were euthanized due to chronic respiratory disease that was unresponsive to treatment. Massive lymphocytic infiltration of the lung interstitium suggested a diagnosis of STLV-associated lymphoma. In each case, the diagnosis was confirmed through inverse PCR (IPCR) that detected monoclonally integrated STLV1 provirus in cellular DNA extracted from lymphoma tissue and peripheral blood cells (PBC). One dominant STLV1-infected T-cell clone and 3 minor clones were detected in PBC from each baboon. Using archived PBC DNA and primers within the proviral genome and chromosomal DNA flanking the STLV1 integration sites in PCR analyses, we determined that the dominant clone in one baboon had first appeared approximately 8 mo after infection and had circulated for 4 y before clinical disease developed. ELISA testing of archived serum revealed that both baboons seroconverted to the p19 and p24 gag proteins and the envelope gp46 protein but not to the viral tax protein. Titers to p24 and gp46 rose significantly after infection and remained relatively constant until death, whereas titers to p19 increased with time. Although spontaneous STLV1-associated lymphomas have been described in baboons, the STLV1-associated lymphomas described here occurred in 2 relatively young baboons, both of whom had become infected with STLV at 3 to 4 y of age and developed lymphoma within 5 y of infection.

摘要

两只自然感染1型猿猴嗜T淋巴细胞病毒(STLV1)的年轻雌性狒狒因对治疗无反应的慢性呼吸道疾病而实施安乐死。肺间质大量淋巴细胞浸润提示诊断为STLV相关淋巴瘤。在每例病例中,通过反向PCR(IPCR)确诊,该方法在从淋巴瘤组织和外周血细胞(PBC)提取的细胞DNA中检测到单克隆整合的STLV1前病毒。在每只狒狒的PBC中检测到1个主要的STLV1感染T细胞克隆和3个次要克隆。在PCR分析中,使用存档的PBC DNA以及前病毒基因组内和STLV1整合位点侧翼的染色体DNA中的引物,我们确定一只狒狒中的主要克隆在感染后约8个月首次出现,并在临床疾病发生前已循环4年。对存档血清进行ELISA检测发现,两只狒狒均出现针对p19和p24 gag蛋白以及包膜gp46蛋白的血清转化,但未出现针对病毒tax蛋白的血清转化。感染后针对p24和gp46的滴度显著升高,并在死亡前保持相对稳定,而针对p19的滴度随时间增加。虽然在狒狒中已描述过自发性STLV1相关淋巴瘤,但此处描述的STLV1相关淋巴瘤发生在2只相对年轻的狒狒身上,它们均在3至4岁时感染STLV,并在感染后5年内发生淋巴瘤。

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