【摘要】： 本研究針對近年來北京地區(qū)腎綜合征出血熱(HFRS)發(fā)病日趨上升的疫情形勢，就宿主動物、毒株特點及HFRS病人感染漢坦病毒(HV)的特征等方面進行了系統(tǒng)的分子流行病學調(diào)查研究。 首先選取近年來發(fā)病較高的海淀區(qū)城鄉(xiāng)結(jié)合部作為調(diào)查點，捕捉宿主動物，運用現(xiàn)代分子生物學檢測手段，基本確定這一地區(qū)優(yōu)勢宿主為褐家鼠，主要流行株是與S3亞型代表株Z37親緣關系較近的的Seoul病毒。 然后從褐家鼠肺組織中分離了漢坦病毒，并對其中的BjHD01株M和S全基因序列進行了測定和分析。結(jié)果顯示，它與其他Seoul病毒的基因序列基本相似，但其氨基酸序列具有獨有特征。系統(tǒng)發(fā)育分析提示，北京地區(qū)毒株在其進化史上可能與不同來源的Seoul病毒存在廣泛的交互作用。 通過病例感染病毒的分子流行病學調(diào)查研究提示在北京地區(qū)治療的病人包括兩部分：于外地感染在京治療者及本地感染治療者。北京地區(qū)Seoul病毒流行株可分為兩個基因簇，一簇分布于北京西南、西北近郊和城市中心地區(qū)，另一簇分布于北京東北近郊和西北遠郊地區(qū)，兩簇在朝陽和順義的交界區(qū)附近交叉分布。 北京市不同發(fā)病狀況的地區(qū)流行毒株各有其獨有的氨基酸特征。小家鼠雖然能夠感染Seoul病毒，，但由于其體內(nèi)病毒發(fā)生的變異，作為傳播宿主的地位可能有限。無論是在動物宿主體內(nèi)還是在病人體內(nèi)，Seoul病毒均以變異混合體(Quasispcies)形式生存，其S片段3’末端均可發(fā)生末端序列缺失，這可能是病毒適應環(huán)境的機制之一。但缺失堿基數(shù)在人體和動物宿主體內(nèi)可能不同，還有待于進一步研究。 本研究針對北京地區(qū)疫情形勢從宿主、病原、病人三個角度、不同層面進行了系統(tǒng)的分子流行病學調(diào)查研究，對北京地區(qū)漢坦病毒的基因特征、感染來源、分布和流行規(guī)律進行了全面分析，深入探討了北京近年來HFRS疫情攀升及病例分布不均衡的主要原因及病毒的適應機制、變異特點，為制定科學、有效的預防和控制措施提供了理論基礎和決策依據(jù)。
[Abstract]:This study aimed at the increasing epidemic situation of hemorrhagic fever with renal syndrome (HFRS) in Beijing area in recent years. The characteristics of strain and the characteristics of Hantavirus (HV) infection in HFRS patients were investigated systematically by molecular epidemiology. Firstly, the urban and rural areas with high incidence in recent years were selected as the investigation points to capture host animals and to determine the dominant host of Rattus norvegicus basically by means of modern molecular biological detection. The main epidemic strain is Seoul virus, which is closely related to the representative strain Z37 of S3 subtype. Then Hantavirus was isolated from the lung tissue of Rattus norvegicus and the M and S gene sequences of BjHD01 strain were determined and analyzed. The results showed that its amino acid sequence was similar to that of other Seoul viruses, but its amino acid sequence had unique characteristics. Phylogenetic analysis suggested that the strains in Beijing might interact with Seoul viruses from different sources in their evolutionary history. The molecular epidemiologic investigation of cases of viral infection indicated that the patients treated in Beijing included two parts: those who had been treated in Beijing and those who had been treated in Beijing. The Seoul virus epidemic strains in Beijing can be divided into two clusters, one is in southwest Beijing, the other is in northwest suburb and urban center area, the other is located in northeast suburb and northwest suburb of Beijing. The two clusters are intersected near the junction of Chaoyang and Shunyi. The epidemic strains in different areas of Beijing have their unique amino acid characteristics. Although mice can infect Seoul virus, their status as a transmission host may be limited due to the variation of the virus in their bodies. Both in animal host and in patient, Seoul virus survives in the form of variant (Quasispcies), and its S fragment 3 'end can cause terminal deletion, which may be one of the mechanisms of virus adaptation to the environment. However, the number of missing bases may be different in human and animal hosts, which needs further study. In this study, a systematic molecular epidemiological investigation on the epidemic situation in Beijing was carried out from three aspects: host, pathogen and patient. The genetic characteristics and source of Hantavirus infection in Beijing were studied. The distribution and epidemic law were comprehensively analyzed, and the main causes of the rising HFRS epidemic situation and uneven distribution of cases in Beijing in recent years, as well as the adaptive mechanism and variation characteristics of the virus, were discussed in depth. Effective prevention and control measures provide the theoretical basis and decision-making basis.
【學位授予單位】：中國人民解放軍軍事醫(yī)學科學院
【學位級別】：博士
【學位授予年份】：2007
【分類號】：R512.8;R181.3

【引證文獻】

相關碩士學位論文 前1條

1 劉勇;以滅活純化腎綜合征出血熱疫苗為主的干預模式的流行病學效果評價[D];山東大學;2012年

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