MOUSE ADENOVIRUS TYPE-1 CAUSES A FATAL HEMORRHAGIC ENCEPHALOMYELITIS IN ADULT C57BL/6 BUT NOT BALB/C MICE
MOUSE ADENOVIRUS TYPE-1 CAUSES A FATAL HEMORRHAGIC ENCEPHALOMYELITIS IN ADULT C57BL/6 BUT NOT BALB/C MICE
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DOI：
10.1128/jvi.69.12.7674-7681.1995
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发表时间：
1995-12-01
影响因子：
5.4
通讯作者：
HORWITZ, MS
中科院分区：
文献类型：
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作者：
GUIDA, JD;FEJER, G;HORWITZ, MS
1型小鼠腺病毒（MAV-1）可引起新生小鼠或乳鼠的一种致死性疾病，其特征为感染性病毒和多个器官的病毒损伤。然而，我们目前的结果表明，MAV-1在成年CS 7 BL/6（B6）小鼠中引起致命性疾病（50%致死剂量，[LD（50）]，10（3.0）PFU），但在所有测试剂量下（LD（50）大于或等于10（5.0）PFU），成年BALB/c小鼠中均未引起致命性疾病。成年（BALB/c x B6）F-1小鼠为中度易感（LD（50），10（4.5）PFU）。临床上，敏感的B6小鼠表现出急性中枢神经系统（CNS）疾病的症状，包括震颤、癫痫发作、共济失调和瘫痪。来自B6动物的CNS组织的光学显微镜检查显示脑酸性脊髓中的点状出血、水肿、新血管形成和轻度炎症。电子显微镜分析显示炎症证据，如活化的小胶质细胞，以及肿胀的星形胶质细胞终足和血管周围脂质沉积，表明血脑屏障功能障碍。在CNS外，唯一显著的病理学发现是脾白色髓中的细胞溶解灶，通过使用RNA酶保护测定用反义MAV-1早期区1a探针进行来自多种组织的病毒复制的评估，在MAV-1感染的B6动物中，最大量的病毒mRNA位于脑和脊髓中，在脾、肺和心脏中检测到较少的病毒信息。在BALB/c小鼠组织中没有检测到病毒mRNA，除了心脏中的低水平。还测定了器官组织的病毒滴度，并且与脑和脊髓上的RNA酶保护结果一致，但未能证明在其他器官中有显著的感染性病毒。我们的实验证明MAV-1对CNS具有显著的嗜性，这是菌株依赖性的，这为腺病毒发病机制的研究提供了信息丰富的体内模型。
Mouse adenovirus type 1 (MAV-1) produces a lethal disease in newborn or suckling mice characterized by infectious virus and viral lesions in multiple organs, Previous reports of MAV-1 infection of adult mice generally described serologic evidence of infection without morbidity or mortality. However, our current results demonstrate that MAV-1 causes a fatal illness in adult CS7BL/6 (B6) mice (50% lethal dose, [LD(50)], 10(3.0) PFU) but not in adult BALB/c mice at all of the doses tested (LD(50) greater than or equal to 10(5.0) PFU). Adult (BALB/c x B6)F-1 mice were intermediately susceptible (LD(50), 10(4.5) PFU). Clinically, the sensitive B6 mice showed symptoms of acute central nervous system (CNS) disease, including tremors, seizures, ataxia, and paralysis, Light microscopic examination of CNS tissue from the B6 animals revealed petechial hemorrhages, edema, neovascularization, and mild inflammation in the brain acid spinal cord. Analysis by electron microscopy showed evidence of inflammation, such as activated microglia, as well as swollen astrocytic endfeet and perivascular lipid deposition indicative of blood-brain barrier dysfunction, Outside of the CNS, the only significant pathological findings were foci of cytolysis in the splenic white pulp, Assessment of viral replication from multiple tissues was performed by using RNase protection assays with an antisense MAV-1 early region la probe, The greatest amounts of viral mRNA in MAV-1-infected B6 animals were located in the brain and spinal cord, Less viral message was detected in the spleen, lungs, and heart. No viral mRNA was detected in BALB/c mouse tissue, with the exception of low levels in the heart, Viral titers of organ tissues were also determined and were concordant with RNase protection findings on the brain and spinal cord but failed to demonstrate significant infectious virus in additional organs, Our experiments demonstrate that MAV-1 has a striking tropism for the CNS that is strain dependent, and this provides an informative in vivo model for the study of adenoviral pathogenesis.