Molecular design and construction of infection protective antigens for Q fever agent

我们使用一种新的Q热的SCID小鼠动物实验模型来研究伯氏柯克斯体不同菌株之间的差异。一株慢性毒株对SCID小鼠的致病性与急性毒株完全不同。慢性Q热的原型菌株伯氏梭菌普里西拉株对SCID小鼠造成的心脏损害没有预期的严重。感染Priscilla株的SCID小鼠临床病程长而轻，组织病理学观察较轻。结果表明，Q热的表现与病原因素和宿主因素有关。然后，我们对72株日本分离株的ICD、NAD、COM1基因进行了PCR-RFLP分析。49株分离物的PCR-RFLP图谱与国外报道的不同，与已发表的ICD基因图谱相同。日本的各种异构体的序列与已发表的数据不同。日本不同分离株的氨基酸序列与无质粒的合体株完全相同。我们的项目使SCID小鼠可用于Q热的动物模型，建立了检测Q热抗原和抗体的乳胶凝集试验，以及日本分离的布氏梭菌的分子特性，这应该与国外的分离株有所不同。

We investigated differences among Coxiella burnetii strains using a new animal experiment model of SCID mice for Q fever. Pathogenicity of a chronic strains in SCID mice was completely different from that of the acute strain. The severity of the heart lesion in SCID mice caused by C. burnetii Priscilla strain, the prototype strain for chronic Q fever, were less severe than expected. The clinical course of SCID mice infected with Priscilla strain was long and mild, and the histopathological observations were mild. The results suggest that pathogen factors as well as host factors are involved in the manifestation of Q fever.Then we investigated PCR-RFLP on icd nad, com1 genes for 72 isolates in Japan. Fourty-nine isolates showed varied PCR-RFLP, which was reported on isoates overseas, to other isolates which showed the same profile as published pattern on icd gene. Sequences of the varied isoates in Japan were different from those of published data. Putative amino acid sequences of the varied isolates in Japan were identical to those of plasmid-less choric strains~. We showed the presence of unique strains in Japan.Our project resulted in the usefulness of SCID mice for an animal model of Q fever, the establishment of Latex agglutination assay for detecting antigen and antibody of Q fever, and molecular properties of C. burnetii isolates in Japan which should be different from those of overseas isolates.