Jaeckel E, Heringlake S, Berger D, Brabant G, Hunsmann G, Manns M P
Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany.
Diabetes. 1999 Jan;48(1):209-14. doi: 10.2337/diabetes.48.1.209.
In the past, endogenous retroviral sequences have been isolated from patients suffering from different kinds of autoimmune diseases. Recently, a full length retroviral genome, termed IDDMK(1,2)22, was isolated from patients with new-onset IDDM. This genome contains a major histocompatibility complex II-dependent superantigen within its envelope gene. The viral sequence was found in ten patients with new-onset IDDM, but not in age-matched control subjects (Conrad et al. [9]). We searched for the presence of this viral genome by nested reverse transcription-polymerase chain reaction (RT-PCR) in a cohort of six patients with new-onset IDDM and six control subjects of the same age. We found all samples to be positive without any differences between patients and control subjects. The same results were obtained with supernatants of activated peripheral blood mononuclear cells. We performed isopycnic ultracentrifugation in sucrose density gradients on all samples and were unable to detect particles of the new virus in any of our samples. However, positive signals were obtained from all pellet fractions. RNase, DNase treatment and nested PCRs without reverse transcription showed that the positive signals were probably derived from intracellular RNA and DNA. In summary, no correlation between a positive nested PCR signal for IDDMK(1,2)22 and diabetes was found indicating that the new sequence represents just an additional member of the human endogenous retrovirus (HERV) family with lack of an exogenous counterpart.
过去,已从患有各种自身免疫性疾病的患者中分离出内源性逆转录病毒序列。最近,从新发胰岛素依赖型糖尿病(IDDM)患者中分离出一个全长逆转录病毒基因组,称为IDDMK(1,2)22。该基因组在其包膜基因内含有一个主要组织相容性复合体II依赖性超抗原。在10例新发IDDM患者中发现了该病毒序列,但在年龄匹配的对照受试者中未发现(康拉德等人[9])。我们通过巢式逆转录-聚合酶链反应(RT-PCR)在一组6例新发IDDM患者和6例同龄对照受试者中寻找该病毒基因组的存在情况。我们发现所有样本均为阳性,患者和对照受试者之间没有任何差异。活化外周血单核细胞的上清液也得到了相同的结果。我们对所有样本进行了蔗糖密度梯度等密度超速离心,在任何样本中均未检测到新病毒颗粒。然而,所有沉淀组分均获得了阳性信号。核糖核酸酶、脱氧核糖核酸酶处理以及无逆转录的巢式PCR表明,阳性信号可能源自细胞内RNA和DNA。总之,未发现IDDMK(1,2)22的巢式PCR阳性信号与糖尿病之间存在相关性,这表明该新序列只是人类内源性逆转录病毒(HERV)家族的另一个成员,不存在外源性对应物。