Molecular mechanisms of infection and pathogenesis of viruses

病毒感染和发病的分子机制

• 批准号: 08406020
• 负责人: KIDA Hiroshi
• 金额: $ 20.29万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08406020/
• 关键词: influenza virus; pathogenicity; host cell factor; vascular endothelial cell; blood coagulation factor; disseminated intravascular coagulation; chicken; 血管内血液凝固; マウス; ヘマグルチニン; モノクローナル抗体; ニューキャッスル病ウイルス; F蛋白; HN蛋白; 温度感受性; ウイルス; 宿主因子; インフルエンザ

Intravenous injection into chickens with the virus-free extracts from the allantoic membrane of chicken embryos infected with influenza viruses resulted in sudden death due to blood coagulation in the vessels. The chickens injected intravenously with heparin prior to the injection with the extract survived without any signs of disease. The results suggest that some coagulation factors exist in the tissues where virus replicated and that they showed toxiciry to the chickens.To provide information on the pathogenically of fowl plague virus, virological and histopathological comparison was carried out between chickens experimentally infected with virulent and avirulent influenza virus strains. Virulent viruses replicated extensively in the vascular endothelial cells after viremia, whereas avirulent viruses were limited to replicate in the respiratory tracts. Virulent viruses induced severe damage to the vascular walls (vasculitis), leading to the abnormal coagulation of the blood as well as hyperemia, edema and breakdown of the blood-brain barrier. These findings together with the results of biological analyses on infected tissue extracts indicate that the vasculitis-mediated host factors cause the disease signs of fowl plague.

将感染流感病毒的鸡胚尿囊膜的无病毒提取物静脉注射到鸡体内，由于血管中的血液凝固而导致猝死。在注射浸提液之前静脉注射肝素的鸡存活，没有任何疾病迹象。结果表明，在病毒复制的组织中存在着某些凝血因子，它们对鸡有毒性作用，为进一步了解禽瘟病毒的致病性，本研究对禽流感病毒强毒株和弱毒株人工感染鸡进行了病毒学和组织病理学的比较。病毒血症后，毒力强的病毒在血管内皮细胞中广泛复制，而无毒力的病毒仅限于在呼吸道中复制。毒病毒引起血管壁的严重损伤（血管炎），导致血液异常凝固以及充血、水肿和血脑屏障的破坏。这些发现以及对感染组织提取物的生物学分析结果表明，血管炎介导的宿主因素引起了家禽鼠疫的疾病体征。

项目成果

T.Ito: "Molecular basis for the generation in pigs of influenza A viruses with pandemic potential." J.Virol.72. 7367-7373 (1998)

T.Ito：“猪体内产生具有大流行潜力的甲型流感病毒的分子基础。”

A.Vines: "The role of residues 226 and 228 of influenza A virus hemagglutinin in receptor specificity and host range restriction." J.Virol.72. 7626-7631 (1998)

A.Vines：“甲型流感病毒血凝素残基 226 和 228 在受体特异性和宿主范围限制中的作用。”

M.Imai, et al.: "Antigenic and genetic analyses of H5 influenza viruses isolated from wild ducks in Asia." Jpn.J.Vet.Res.46. 171-177 (1999)

M.Imai 等人：“从亚洲野鸭中分离出的 H5 流感病毒的抗原和遗传分析。”

Takakuwa,H.: "An attenuation mechanism of Newcastle disease vaccine strain TCND." Arch.Virol.(in press). (1998)

Takakuwa,H.：“新城疫疫苗株 TCND 的减毒机制。”

Shortridge,K.F.: "Characterization of Avian H5N1 Influenza Viruses from Poultry in Hong Kong." Virology. 252. 331-342 (1998)

Shortridge, K.F.：“香港家禽中禽 H5N1 流感病毒的特征。”