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中國(guó)狂犬病2007年流行特征及病毒N基因分子流行病學(xué)研究

發(fā)布時(shí)間:2018-04-24 19:18

  本文選題:狂犬病 + 狂犬病病毒; 參考:《中國(guó)疾病預(yù)防控制中心》2010年碩士論文


【摘要】: 狂犬病是由狂犬病毒感染引起的一種人獸共患的烈性傳染病,病死率幾乎為100%。許多動(dòng)物既是儲(chǔ)存宿主又作為傳播媒介在世界范圍內(nèi)維系并傳播著本病。近年來(lái)狂犬病在我國(guó)持續(xù)高發(fā),2003突破2000例,2007年發(fā)病死亡人數(shù)已達(dá)到3302例,除青海、西藏外其余29個(gè)省、區(qū)均有病例報(bào)告。近年在狂犬病高發(fā)省區(qū)開(kāi)展了一系列的調(diào)查研究,但對(duì)于中、低發(fā)地區(qū)疫情的快速上升和地域性擴(kuò)散尚未引起足夠的重視,也缺乏相應(yīng)的調(diào)查。為此,本研究在以往工作的基礎(chǔ)上,分析了我國(guó)2007年狂犬病疫情特征,根據(jù)我國(guó)狂犬病病例的流行和地理分布情況選擇流行程度不同的七個(gè)省(自治區(qū)、直轄市)收集標(biāo)本,檢測(cè)和分析不同宿主動(dòng)物感染狂犬病病毒及病毒N基因遺傳變異狀況,通過(guò)與高發(fā)病地區(qū)調(diào)查結(jié)果進(jìn)行比較,探討我國(guó)狂犬病高、中和低發(fā)病地區(qū)狂犬病的流行和分布和狂犬病病毒遺傳變異間關(guān)系,為更為有效控制狂犬病疫情的蔓延提供科學(xué)依據(jù)。 2007年狂犬病疫情分析顯示我國(guó)狂犬病流行繼續(xù)升高并呈現(xiàn)從南部向北部、從高發(fā)向低發(fā)地區(qū)蔓延的趨勢(shì),病例以夏秋季節(jié)為多、男性多于女性。在狂犬病流行程度不同的七個(gè)省收集了382份不同宿主動(dòng)物來(lái)源的組織標(biāo)本,經(jīng)直接免疫熒光法和RT-PCR兩種方法檢測(cè)出狂犬病毒感染陽(yáng)性的標(biāo)本81份,選擇N基因編碼區(qū)下游720個(gè)(634-1353位)核苷酸序列進(jìn)行擴(kuò)增和測(cè)序,獲得34份病毒標(biāo)本相應(yīng)區(qū)段的核苷酸序列;蛐蛄型葱苑治鼋Y(jié)果:34個(gè)N基因核苷酸序列同源性為87.5-100%,推導(dǎo)的氨基酸序列同源性為93.3-99.6%,表明該區(qū)段核苷酸序列的變異主要是同義突變。N蛋白該區(qū)段氨基酸序列包含Ⅰ、Ⅲ、Ⅳ個(gè)抗原位點(diǎn)及Th細(xì)胞表位,34個(gè)病毒標(biāo)本N基因的這些功能位點(diǎn)都高度保守,而且在該氨基酸區(qū)段都具有389位絲氨酸磷酸化位點(diǎn)和375位蘇氨酸次要磷酸化位點(diǎn),提示N基因功能位點(diǎn)的保守性與N基因的遺傳穩(wěn)定性有關(guān)。 N基因核苷酸序列種系發(fā)生樹(shù)分析顯示,34個(gè)病毒標(biāo)本都屬于基因Ⅰ型狂犬病毒,具有按來(lái)源省份不同進(jìn)一步進(jìn)化為不同群或亞群的地域性特征,且存在野生動(dòng)物與家養(yǎng)動(dòng)物間的相互感染與傳播。在進(jìn)化趨勢(shì)上存在由西南地區(qū)向中部地區(qū)進(jìn)而向東部地區(qū)和東南部地區(qū)傳播流行的可能性;與近幾年狂犬病地域分布和擴(kuò)散趨勢(shì)相吻合,說(shuō)明我國(guó)狂犬病的流行與狂犬病病毒的分布和傳播有著直接的關(guān)系。在與國(guó)際毒株的比較分析中,所有我國(guó)標(biāo)本(Ⅰ、Ⅱ、Ⅲ群)都集中在一個(gè)大分支下,表明我國(guó)狂犬病病毒區(qū)別于其它國(guó)家的病毒,基本在本國(guó)及周邊地區(qū)循環(huán)。在中國(guó)分支下,還包含印度尼西亞和泰國(guó)這兩個(gè)亞洲國(guó)家的2株狂犬病病毒,其中Ⅱ群的云南毒株與泰國(guó)犬分離株存在極近的親緣關(guān)系,而與其他33個(gè)本國(guó)毒株(Ⅰ、Ⅲ群)的親緣關(guān)系相對(duì)較遠(yuǎn),結(jié)合歷史背景及多方面因素分析,東南亞和我國(guó)之間極可能存在著狂犬病病毒的交互感染和傳播。 研究結(jié)果表明,我國(guó)狂犬病近幾年疫情繼續(xù)升高并呈現(xiàn)地域性擴(kuò)散,狂犬病病毒的傳播和擴(kuò)散可能是造成疫情快速上升和流行區(qū)域擴(kuò)大的原因之一。我國(guó)狂犬病病毒N基因核苷酸變異呈現(xiàn)地域特征,其編碼蛋白上的抗原位點(diǎn)均高度保守;N基因種系發(fā)生樹(shù)分析顯示這些地區(qū)流行的均為基因Ⅰ型狂犬病病毒,并且來(lái)源于同一省份的病毒顯示出更高的親緣特性。病毒標(biāo)本間進(jìn)化關(guān)系結(jié)合流行病學(xué)背景顯示,我國(guó)野生動(dòng)物與家養(yǎng)動(dòng)物之間,本國(guó)動(dòng)物與鄰國(guó)動(dòng)物之間,可能均存在著狂犬病毒的交叉感染和傳播。 本研究通過(guò)對(duì)我國(guó)狂犬病流行程度不同的地區(qū)野生動(dòng)物和家養(yǎng)動(dòng)物間狂犬病毒流行株的N基因分子特征進(jìn)行了深入詳細(xì)的分析,探討了我國(guó)狂犬病病毒遺傳變異特點(diǎn)及其與流行的關(guān)系,以便為更加科學(xué)地制定我國(guó)狂犬病預(yù)防控制措施提供科學(xué)依據(jù)。
[Abstract]:Rabies is a kind of zoonotic infectious disease caused by rabies virus infection. The mortality rate is almost 100%.. Many animals are both the host and the media in the world. In recent years, the incidence of rabies in China, 2003 breakthroughs in 2000 cases, and the number of deaths in 2007 have reached 3302. In Qinghai and the other 29 provinces and regions outside Tibet, case reports have been reported. In recent years, a series of investigations have been carried out in the provinces of high incidence of rabies. However, the rapid rise and regional spread of the epidemic in low hair areas has not yet aroused enough attention and lack of corresponding investigation. On the basis of previous work, this study has analyzed China's 2007. According to the epidemic and geographical distribution of rabies cases in China, seven provinces (autonomous regions and municipalities directly under the central government) were selected according to the prevalence and geographical distribution of rabies cases in China. The genetic variation of rabies virus and N gene in different host animals was detected and analyzed, and the results were compared with the results of the high incidence area. The relationship between rabies epidemic and distribution and the genetic variation of rabies virus in high rabies, middle and low incidence areas provides a scientific basis for more effective control of the spread of rabies.
Analysis of the outbreak of rabies in 2007 showed that the trend of rabies prevalence in China continued to rise and spread from the south to the north, from high to low hair areas, with more cases in summer and autumn, more males than women. In seven provinces of different rabies prevalence, 382 tissues from different host animals were collected and direct immunofluorescence was used. 81 specimens of rabies virus infection were detected by two methods of light and RT-PCR, and 720 (634-1353) nucleotide sequences of the N gene coding region were amplified and sequenced, and 34 nucleotide sequences of the virus specimens were obtained. The homology analysis results of the gene sequence: the nucleotide sequence of 34 N genes was 87.5-100%, The deduced amino acid sequence homology is 93.3-99.6%, which indicates that the variation of the nucleotide sequence of the region is mainly synonymous mutation.N protein. The amino acid sequence of the section contains I, III, IV antigen sites and Th cell epitopes, and these functional sites of the 34 virus specimens are highly conserved, and there are 389 silk ammonia in the amino acid section. Acid phosphorylation sites and 375 threonine secondary phosphorylation sites suggest that the conservatism of N gene functional sites is related to the genetic stability of N gene.
The nucleotide sequence tree analysis of the N gene showed that all the 34 virus specimens belonged to the type I rabies virus, which had the regional characteristics of further evolution to different groups or subgroups according to the different source provinces, and there was mutual infection and transmission between wild animals and domestic animals. The possibility of spreading to the eastern region and the southeast region, which is consistent with the regional distribution and diffusion trend of rabies in recent years, shows that there is a direct relationship between the prevalence of rabies and the distribution and transmission of rabies virus in China. In comparison with international strains, all Chinese specimens (I, II, and group III) are concentrated in the analysis. A large branch shows that rabies virus in our country is different from other countries and circulates basically in the country and its surrounding areas. Under China's branch, there are 2 rabies viruses in two Asian countries, including Indonesia and Thailand, of which the Yunnan and Thailand isolates of group II are closely related to the Thailand canine isolates, with the other 3. The relationship of 3 native strains (I, III group) is relatively distant. According to the historical background and the analysis of many factors, the interaction and transmission of rabies virus may exist in Southeast Asia and China.
The results show that the epidemic situation of rabies in China continues to rise in recent years and presents regional diffusion. The spread and diffusion of rabies virus may be one of the reasons for the rapid increase of the epidemic situation and the expansion of the epidemic area. The nucleotide variation of the N gene of rabies virus in our country presents regional characteristics and the antigen loci on the encoded protein are highly conservative. The N gene phylogenetic tree analysis showed that all of these regions were prevalent in the region of type I rabies virus, and the virus derived from the same province showed higher genetic characteristics. The evolutionary relationship of the virus specimens and the epidemiological background showed that between Chinese wild animals and domestic animals, between domestic animals and neighbouring animals, may be possible. The cross infection and transmission of rabies virus are present.
In this study, the N gene characteristics of wild and domestic rabies virus epidemic strains in different areas of China's rabies epidemic were analyzed in detail. The characteristics of the genetic variation of rabies virus in China and the relationship with the epidemic were discussed in order to make the prevention and control measures of rabies in our country more scientifically. Provide scientific basis for application.

【學(xué)位授予單位】:中國(guó)疾病預(yù)防控制中心
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2010
【分類(lèi)號(hào)】:R512.99;R181.3

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 張姝;不同狂犬疫苗免疫后血清交叉保護(hù)作用研究[D];吉林大學(xué);2013年

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本文編號(hào):1797890

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