人类巨细胞病毒UL144、UL139、UL149基因多态性与其致病性关系的研究
发布时间：2019-04-22 18:09
【摘要】：前言 人类巨细胞病毒(Human cytomegalovirus HCMV)在人群中感染非常普遍,对于免疫功能正常的人来说通常是不显性感染或潜伏感染,但胎儿及免疫缺陷患者感染可导致极高的死亡率。目前关于HCMV感染的发病机制还不十分清楚,我们还不理解为什么在免疫抑制的宿主内,一些CMV感染可导致有症状的各系统疾病,而另一些为无症状的病毒感染。CMV感染或复制数量的高低对于识别高危人群是有作用的,但是CMV数量和预测的临床症状并不完全一致。我的前期研究工作也证实了这一观点。 HCMV基因组具有广范的多态性,这种多态性是否与HCMV特异株的组织嗜性、毒力、免疫逃避机制以及患病群体的临床表现有关还不清楚。以往对HCMV包膜糖蛋白gB的研究最为广泛。早期研究表明gB基因型与HCMV感染的临床表现有关。但是近来一些研究否认了gB蛋白基因的多态性与临床表现、预后及组织嗜性的特异关系。 1996年,Cha等发现在Toledo等低传代临床分离株中有19个开放阅读框架(open reading frame,ORF)的片段在实验室株AD169株中丢失,这些新序列位于长独特序列(UL)与方向重复序列b’(IRL)的交界区(UL/b’区),依次命名为UL133～UL151,此区为高度可变区。目前,19个ORF所编码的蛋白质功能还不十分清楚。推测AD169、Towne等实验室株在细胞培养反复传代过程中出现了UL/b’区遗传信息的丢失和重排,并导致HCMV毒力和致病性的明显减弱,这19个ORF很可能在病毒对宿主的致病力方面起重要作用,是挖掘HCMV感染发病机制的标志基因。 因为HCMV可以感染多个器官和组织,人们产生设想HCMV感染性疾病和组织嗜性可能与菌株的序列变化有关。MacCormac等人的研究证明,HCMV不同分离株在体内确实存在不同的细胞嗜性。表明,引起不同临床
[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.
【学位授予单位】：中国医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363
本文编号：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.
【学位授予单位】：中国医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363
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相关期刊论文 前5条
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