人類巨細(xì)胞病毒UL144、UL139、UL149基因多態(tài)性與其致病性關(guān)系的研究
發(fā)布時間：2019-04-22 18:09
【摘要】：前言 人類巨細(xì)胞病毒(Human cytomegalovirus HCMV)在人群中感染非常普遍,對于免疫功能正常的人來說通常是不顯性感染或潛伏感染,但胎兒及免疫缺陷患者感染可導(dǎo)致極高的死亡率。目前關(guān)于HCMV感染的發(fā)病機(jī)制還不十分清楚,我們還不理解為什么在免疫抑制的宿主內(nèi),一些CMV感染可導(dǎo)致有癥狀的各系統(tǒng)疾病,而另一些為無癥狀的病毒感染。CMV感染或復(fù)制數(shù)量的高低對于識別高危人群是有作用的,但是CMV數(shù)量和預(yù)測的臨床癥狀并不完全一致。我的前期研究工作也證實(shí)了這一觀點(diǎn)。 HCMV基因組具有廣范的多態(tài)性,這種多態(tài)性是否與HCMV特異株的組織嗜性、毒力、免疫逃避機(jī)制以及患病群體的臨床表現(xiàn)有關(guān)還不清楚。以往對HCMV包膜糖蛋白gB的研究最為廣泛。早期研究表明gB基因型與HCMV感染的臨床表現(xiàn)有關(guān)。但是近來一些研究否認(rèn)了gB蛋白基因的多態(tài)性與臨床表現(xiàn)、預(yù)后及組織嗜性的特異關(guān)系。 1996年,Cha等發(fā)現(xiàn)在Toledo等低傳代臨床分離株中有19個開放閱讀框架(open reading frame,ORF)的片段在實(shí)驗(yàn)室株AD169株中丟失,這些新序列位于長獨(dú)特序列(UL)與方向重復(fù)序列b’(IRL)的交界區(qū)(UL/b’區(qū)),依次命名為UL133～UL151,此區(qū)為高度可變區(qū)。目前,19個ORF所編碼的蛋白質(zhì)功能還不十分清楚。推測AD169、Towne等實(shí)驗(yàn)室株在細(xì)胞培養(yǎng)反復(fù)傳代過程中出現(xiàn)了UL/b’區(qū)遺傳信息的丟失和重排,并導(dǎo)致HCMV毒力和致病性的明顯減弱,這19個ORF很可能在病毒對宿主的致病力方面起重要作用,是挖掘HCMV感染發(fā)病機(jī)制的標(biāo)志基因。 因?yàn)镠CMV可以感染多個器官和組織,人們產(chǎn)生設(shè)想HCMV感染性疾病和組織嗜性可能與菌株的序列變化有關(guān)。MacCormac等人的研究證明,HCMV不同分離株在體內(nèi)確實(shí)存在不同的細(xì)胞嗜性。表明,引起不同臨床
[Abstract]:Human cytomegalovirus (Human cytomegalovirus HCMV) infection is very common in the population. It is usually non-dominant infection or latent infection in people with normal immune function. However, infections in fetuses and immunodeficient patients can lead to extremely high mortality rates. At present, the pathogenesis of HCMV infection is not very clear, and we do not understand why in immunosuppressive hosts, some CMV infections can lead to symptomatic systemic diseases. While others are asymptomatic viral infections, the number of CMV infections or replications is useful for identifying high-risk populations, but the number of CMV is not exactly the same as the predicted clinical symptoms. My previous research work has also confirmed this view. There is a wide-ranging polymorphism in the HCMV genome. It is not clear whether this polymorphism is related to the tissue tropism, virulence, immune escape mechanism and clinical manifestation of the HCMV-specific strain. In the past, the study of HCMV envelope glycoprotein gB was the most extensive. Early studies have shown that gB genotypes are associated with clinical manifestations of HCMV infection. However, some recent studies have denied the specific relationship between gB gene polymorphism and clinical manifestations, prognosis and tissue tropism. In 1996, Cha et al found that 19 open reading frames (open reading frame,ORF) fragments in low passage clinical isolates, such as Toledo, were lost in the laboratory strain AD169. These new sequences are located in the junction region (UL/b' region) between the long unique sequence (UL) and the direction repeat sequence b'(IRL). This region is named UL133~UL151, in turn as a highly variable region. At present, the function of the 19 ORF encoded proteins is not very clear. It was speculated that the loss and rearrangement of genetic information in UL/b' region occurred during the repeated passage of cell culture in laboratory strains such as AD169,Towne, which resulted in the obvious weakening of virulence and pathogenicity of HCMV. These 19 ORF may play an important role in the virulence of the virus to the host and are the markers of the pathogenesis of HCMV infection. Because HCMV can infect multiple organs and tissues, it is assumed that HCMV infectious diseases and tissue tropism may be related to the sequence changes of the strains. Mac Cormac et al., have shown that different HCMV isolates do have different cellular tropism in vivo. It is indicated that the cause of the disease is different from clinical.
【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R363
本文編號：2463070
[Abstract]:Human cytomegalovirus (Human cytomegalovirus HCMV) infection is very common in the population. It is usually non-dominant infection or latent infection in people with normal immune function. However, infections in fetuses and immunodeficient patients can lead to extremely high mortality rates. At present, the pathogenesis of HCMV infection is not very clear, and we do not understand why in immunosuppressive hosts, some CMV infections can lead to symptomatic systemic diseases. While others are asymptomatic viral infections, the number of CMV infections or replications is useful for identifying high-risk populations, but the number of CMV is not exactly the same as the predicted clinical symptoms. My previous research work has also confirmed this view. There is a wide-ranging polymorphism in the HCMV genome. It is not clear whether this polymorphism is related to the tissue tropism, virulence, immune escape mechanism and clinical manifestation of the HCMV-specific strain. In the past, the study of HCMV envelope glycoprotein gB was the most extensive. Early studies have shown that gB genotypes are associated with clinical manifestations of HCMV infection. However, some recent studies have denied the specific relationship between gB gene polymorphism and clinical manifestations, prognosis and tissue tropism. In 1996, Cha et al found that 19 open reading frames (open reading frame,ORF) fragments in low passage clinical isolates, such as Toledo, were lost in the laboratory strain AD169. These new sequences are located in the junction region (UL/b' region) between the long unique sequence (UL) and the direction repeat sequence b'(IRL). This region is named UL133~UL151, in turn as a highly variable region. At present, the function of the 19 ORF encoded proteins is not very clear. It was speculated that the loss and rearrangement of genetic information in UL/b' region occurred during the repeated passage of cell culture in laboratory strains such as AD169,Towne, which resulted in the obvious weakening of virulence and pathogenicity of HCMV. These 19 ORF may play an important role in the virulence of the virus to the host and are the markers of the pathogenesis of HCMV infection. Because HCMV can infect multiple organs and tissues, it is assumed that HCMV infectious diseases and tissue tropism may be related to the sequence changes of the strains. Mac Cormac et al., have shown that different HCMV isolates do have different cellular tropism in vivo. It is indicated that the cause of the disease is different from clinical.
【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R363
【參考文獻(xiàn)】
相關(guān)期刊論文 前5條
1 何蓉,阮強(qiáng),吉耀華,劉慶,陳淑榮,劉蘭青,呂繩敏;人類巨細(xì)胞病毒UL144基因在臨床低傳代分離株中的多態(tài)性研究[J];中華微生物學(xué)和免疫學(xué)雜志;2003年01期
2 齊瑩,盧穎,馬艷萍,阮強(qiáng),何蓉,吉耀華,劉慶,陳淑榮;人巨細(xì)胞病毒UL138～142基因在臨床低傳代分離株中的多態(tài)性研究[J];中華微生物學(xué)和免疫學(xué)雜志;2004年03期
3 陳雷鈴,胡廷澤,劉繼紅,孟海英,郎詩明,金先慶;先天性巨結(jié)腸癥與人類巨細(xì)胞病毒感染[J];中華小兒外科雜志;2002年03期
4 黃金獅,鄒音,徐本源,朱小春,鐘華生;巨細(xì)胞病毒蛋白在先天性巨結(jié)腸組織中的表達(dá)[J];中華胃腸外科雜志;2004年03期
5 毛志芹,董亞珞,孫梅;定量分析巨細(xì)胞病毒肝炎嬰兒尿液CMV-DNA的臨床意義[J];中國優(yōu)生與遺傳雜志;2005年03期
，本文編號：2463070
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