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人源SARS病毒果子狸感染模型研究

发布时间:2018-07-18 14:18
【摘要】:2002年11月16日,首例SARS患者在中国广东发生,随后蔓延到30多个国家和地区,对人类健康造成严重威胁。2003年4月16同,世界卫生组织根据多个实验室研究结果,确认一种全新的冠状病毒是SARS疾病的病原,这种冠状病毒不属于已知的任何一种冠状病毒,命名为SARS相关冠状病毒(SARS-COV)。 根据流行病学调查,普遍认为SARS病毒很可能来源于动物。2003年5月23日,香港大学与深圳疾控中心联合调查组宣布在果子狸体内检测到SARS样病毒,分离到的病毒基因组序列与人SARS病毒99%同源。农业部动物冠状病毒疫源调查组从果子狸、水蛇、果蝠和猕猴的咽拭子或肛拭子中检测到SARS样病毒核酸,所扩基因为S1、NP和M基因,测序结果与SARS病毒基因同源性在96%-100%之间;血清学检测显示果子狸、水蛇、果蝠、穿山甲等动物部分血清呈SARS病毒抗体阳性反应。基于这此调查结果,果子狸成为传播SARS的最大嫌疑。 果子狸对SARS病毒的易感性是判断果子狸能否成为SARS传播来源的关键依据,本研究用SARS病毒GZ01、BJ01株分别接种果子狸,观察临床症状、剖检与病理组织学变化,并用套式RT-PCR方法和病毒分离方法检测感染果子狸的咽拭子、肛拭子、血液样品及各器官组织,研究果子狸带毒、排毒、病毒在体内分布以及抗体产生等规律。根据实验结果,判断果子狸对人源SARS病毒的易感性,结合野生动物血清学调查等研究成果,综合分析推断果子狸在SARS病毒传播中的作用,从而为SARS病毒的来源研究提供科学依据,同时评价果子狸作为新的SARS研究动物模型的可行性。研究结果如下: 1 接种GZ01和BJ01毒株的果子狸在24-48小时开始发热,发热症状明显、稳定,持续6-16天不等,B组比A组体温升高强度较大,发热持续时间也较长。果子狸发热的同时伴随有精神沉郁、食欲减退等症状,个别发生腹泻症状。
[Abstract]:On November 16, 2002, the first SARS case occurred in Guangdong, China, and then spread to more than 30 countries and regions, posing a serious threat to human health. A novel coronavirus was identified as the causative agent of SARS. This coronavirus is not a known coronavirus and is named SARS-COV. According to epidemiological investigations, it is generally believed that the SARS virus may have originated in animals. On May 23, 2003, the Joint investigation team of the University of Hong Kong and the Shenzhen CDC announced that the SARS-like virus had been detected in the beaver. The genome sequence of the isolated virus was 99% homologous to that of human SARS virus. SARS-like virus nucleic acid was detected from throat swabs or anal swabs of beaver, water snake, fruit bat and rhesus monkey by the investigation of animal coronavirus of Ministry of Agriculture. The nucleic acid of SARS-like virus was amplified by S1-NP and M gene. The result of sequencing was between 96% and 100% homology with SARS virus gene. Serological tests showed that the sera of some animals, such as civets, water snakes, fruit bats and pangolins, were positive for SARS virus antibodies. Based on the findings, the civets became the biggest suspect in the spread of SARS. The susceptibility of civets to SARS virus is the key to judge whether the civets can become the source of SARS transmission. In this study, we inoculated the civets with GZ01and BJ01 strain of SARS virus, and observed the clinical symptoms, autopsy and histopathological changes. The throat swabs, anal swabs, blood samples and tissues of infected civets were detected by nested RT-PCR and virus isolation methods. According to the experimental results, the susceptibility of civets to human SARS virus was judged, and combined with the research results of wild animal serological investigation, the role of civets in the transmission of SARS virus was comprehensively analyzed and inferred. It provides scientific basis for the study of the origin of SARS virus and evaluates the feasibility of the civets as a new animal model for SARS research. The results were as follows: 1 the civets inoculated with GZ01 and BJ01 began to febrile from 24 to 48 hours, and the symptoms of fever were obvious and stable. The body temperature in group B was higher than that in group A for 6-16 days, and the fever lasted longer. Civets fever accompanied by depression, loss of appetite and other symptoms, individual diarrhea symptoms.
【学位授予单位】:沈阳农业大学
【学位级别】:硕士
【学位授予年份】:2005
【分类号】:R181.3

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