INFECTION OF PERIPANCREATIC LYMPH-NODES BUT NOT ISLETS PRECEDES KILHAM RAT VIRUS-INDUCED DIABETES IN BB/WOR RATS
INFECTION OF PERIPANCREATIC LYMPH-NODES BUT NOT ISLETS PRECEDES KILHAM RAT VIRUS-INDUCED DIABETES IN BB/WOR RATS
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DOI：
10.1128/jvi.67.10.5873-5878.1993
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发表时间：
1993-10-01
影响因子：
5.4
通讯作者：
LIKE, AA
中科院分区：
文献类型：
--
作者：
BROWN, DW;WELSH, RM;LIKE, AA
一种血清学鉴定为Kilham大鼠病毒（KRV）的细小病毒可重复诱导糖尿病抗性BB/Wor大鼠的急性I型糖尿病。KRV的组织嗜性进行了研究，通过原位杂交与地高辛标记的质粒DNA探针含有约1.6 kb的基因组的UMass分离的KRV。KRV探针的部分测序显示与小鼠微小病毒的序列（89%）和H1（一种能够感染大鼠和人类的细小病毒）的序列（99%）具有高水平的同源性。在测序的444个碱基中，440个与H1共享。KRV感染后第5天，淋巴组织中可检测到KRV mRNA和DNA，但胰腺中很少检测到。在胸腺、脾脏、胰周和颈部淋巴结中观察到高水平的病毒核酸。在胰腺中观察到的低水平感染基本上仅涉及内皮细胞和间质细胞。胰腺的β细胞未被KRV感染。这些发现表明，KRV广泛感染胰腺周围和其他淋巴组织，但不感染胰腺β细胞，通过扰乱遗传易感性BB/Wor大鼠的免疫系统引发自身免疫性糖尿病。
A parvovirus serologically identified as Kilham rat virus (KRV) reproducibly induces acute type I diabetes in diabetes-resistant BB/Wor rats. The tissue tropism of KRV was investigated by in situ hybridization with a digoxigenin-labelled plasmid DNA probe containing approximately 1.6 kb of the genome of the UMass isolate of KRV. Partial sequencing of the KRV probe revealed high levels of homology to the sequence of minute virus of mice (89%) and to the sequence of H1 (99%), a parvovirus capable of infecting rats and humans. Of the 444 bases sequenced, 440 were shared by H1. KRV mRNA and DNA were readily detected in lymphoid tissues 5 days postinfection but were seldom seen in the pancreas. High levels of viral nucleic acids were observed in the thymus, spleen, and peripancreatic and cervical lymph nodes. The low levels of infection observed in the pancreas involved essentially only endothelial and interstitial cells. Beta cells of the pancreas were not infected with KRV. These findings suggest that widespread infection of peripancreatic and other lymphoid tissues but not pancreatic beta cells by KRV triggers autoimmune diabetes by perturbing the immune system of genetically predisposed BB/Wor rats.