人類巨細胞病毒UL144、UL146和UL147基因多態(tài)性研究
發(fā)布時間：2019-03-02 19:54
【摘要】：目的 小兒先天畸形是影響我國出生人口素質(zhì)的重要因素,宮內(nèi)感染是引起新生兒先天畸形的重要因素之一,而人類巨細胞病毒(Human Cytomagelovirus,HCMV)則在引起先天宮內(nèi)感染的微生物中居于首位。綜合國內(nèi)外研究結(jié)果知,活產(chǎn)新生兒的先天性HCMV感染率約為0.3%-2.3%,平均為1%。先天感染兒中,有癥狀或明顯改變的占5%,有輕微癥狀或非典型癥狀改變的占5%。其余90%HCMV感染表現(xiàn)為亞臨床或慢性感染,這其中5-15%HCMV感染兒多在生后2年內(nèi)發(fā)生神經(jīng)性耳聾或不同程度的神經(jīng)精神運動障礙。HCMV感染引起的先天疾病或畸形主要包括:黃疸性肝炎、膽道閉鎖、先天性巨結(jié)腸等肝膽消化系統(tǒng)疾病或畸形;小頭畸形、智力發(fā)育遲緩等神經(jīng)系統(tǒng)畸形等。部分HCMV先天感染兒也可表現(xiàn)為無癥狀帶毒者。最近研究證明不同的HCMV分離株可在體內(nèi)表現(xiàn)出不同的細胞嗜性。我們以往的研究資料也顯示,神經(jīng)系統(tǒng)畸形患兒HCMV分離株比肝膽消化系統(tǒng)畸形患兒HCMV分離株的首次病毒分離周期短(分別為平均9.5天和19.5天);且HCMV血清抗體與HCMV病毒多肽的反應(yīng)性在不同系統(tǒng)畸形患兒之間存在差異。 目前,HCMV感染的致病機理尚不清楚,大多數(shù)學者認為與病毒的自身結(jié)構(gòu),特別是與病毒的毒力、組織細胞嗜性及其逃避機體免疫能力密切相關(guān)的病毒基因差異,可能是決定HCMV先天感染致病多樣性的重要因素。這些病毒基因的多態(tài)性可能是HCMV致畸、致病的根本原因。因此,針對HCMV不同分離株中與病毒的致病性密切相關(guān)的病毒基因的各項研究已然成為目前國際巨細胞病毒研究最活躍的研究領(lǐng)域。1998年,Wirgart等用DNA測序的方法研究了HCMV基因組中與病毒毒力相關(guān)的直接早期啟動子和增強子、與病毒復(fù)制相關(guān)的DNA聚合酶及與病毒免疫原性相關(guān)的gB蛋白基因等基因序列在不同HCMV臨床分離株之間的差別,雖證實上述差
[Abstract]:Objective congenital malformation in children is an important factor affecting the quality of birth population in China. Intrauterine infection is one of the important factors causing congenital malformation in newborns. Human cytomegalovirus (Human Cytomagelovirus,) is one of the important factors. HCMV) is the leading cause of infection in the prehistoric palace. According to the results of domestic and foreign studies, the congenital HCMV infection rate of live births is about 0.3% ~ 2.3%, with an average of 1%. Of children with congenital infections, 5% had symptoms or significant changes, and 5% had mild or atypical symptoms. The remaining 90%HCMV infections were subclinical or chronic. The congenital diseases or malformations caused by 5-15%HCMV infection mainly include icterohepatitis, biliary atresia, choledochal atresia and choledochal atresia. Congenital Hirschsprung's disease or deformity of hepatobiliary digestive system; Microcephaly, mental retardation and other neurological abnormalities. Some children with congenital HCMV infection may also be asymptomatic carriers. Recent studies have shown that different HCMV isolates exhibit different cellular tropism in vivo. Our previous studies also showed that the first virus isolation cycle of HCMV isolates from children with nervous system malformation was shorter than that of HCMV isolates from children with hepatobiliary and digestive system malformations (mean 9.5days and 19.5days, respectively). Moreover, the reactivity of HCMV serum antibody to HCMV virus polypeptide was different in children with different systemic malformations. At present, the pathogenesis of HCMV infection is not clear. Most scholars believe that the viral gene difference is closely related to the structure of the virus, especially the virulence of the virus, the tropism of tissues and the ability to evade the immunity of the body. It may be an important factor to determine the diversity of congenital infection of HCMV. The polymorphism of these virus genes may be the root cause of teratogenesis and pathogenesis of HCMV. Therefore, various studies on the viral genes closely related to the pathogenicity of viruses in different strains of HCMV have become the most active research field in the field of cytomegalovirus research in the world. Wirgart and others used DNA sequencing method to study the direct early promoter and enhancer related to virus virulence in HCMV genome. Differences of DNA polymerase associated with viral replication and gB protein gene sequences associated with viral immunogenicity among different HCMV clinical isolates, although these differences were confirmed.
【學位授予單位】：中國醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R373
本文編號：2433410
[Abstract]:Objective congenital malformation in children is an important factor affecting the quality of birth population in China. Intrauterine infection is one of the important factors causing congenital malformation in newborns. Human cytomegalovirus (Human Cytomagelovirus,) is one of the important factors. HCMV) is the leading cause of infection in the prehistoric palace. According to the results of domestic and foreign studies, the congenital HCMV infection rate of live births is about 0.3% ~ 2.3%, with an average of 1%. Of children with congenital infections, 5% had symptoms or significant changes, and 5% had mild or atypical symptoms. The remaining 90%HCMV infections were subclinical or chronic. The congenital diseases or malformations caused by 5-15%HCMV infection mainly include icterohepatitis, biliary atresia, choledochal atresia and choledochal atresia. Congenital Hirschsprung's disease or deformity of hepatobiliary digestive system; Microcephaly, mental retardation and other neurological abnormalities. Some children with congenital HCMV infection may also be asymptomatic carriers. Recent studies have shown that different HCMV isolates exhibit different cellular tropism in vivo. Our previous studies also showed that the first virus isolation cycle of HCMV isolates from children with nervous system malformation was shorter than that of HCMV isolates from children with hepatobiliary and digestive system malformations (mean 9.5days and 19.5days, respectively). Moreover, the reactivity of HCMV serum antibody to HCMV virus polypeptide was different in children with different systemic malformations. At present, the pathogenesis of HCMV infection is not clear. Most scholars believe that the viral gene difference is closely related to the structure of the virus, especially the virulence of the virus, the tropism of tissues and the ability to evade the immunity of the body. It may be an important factor to determine the diversity of congenital infection of HCMV. The polymorphism of these virus genes may be the root cause of teratogenesis and pathogenesis of HCMV. Therefore, various studies on the viral genes closely related to the pathogenicity of viruses in different strains of HCMV have become the most active research field in the field of cytomegalovirus research in the world. Wirgart and others used DNA sequencing method to study the direct early promoter and enhancer related to virus virulence in HCMV genome. Differences of DNA polymerase associated with viral replication and gB protein gene sequences associated with viral immunogenicity among different HCMV clinical isolates, although these differences were confirmed.
【學位授予單位】：中國醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R373
【參考文獻】
相關(guān)期刊論文 前4條
1 何蓉,劉蘭青,呂繩敏,阮強;熒光定量PCR方法檢測嬰兒尿液中人類巨細胞病毒基因的含量[J];中華兒科雜志;2001年12期
2 阮強,盧穎,何蓉,吉耀華,齊瑩,劉慶,陳淑榮,馬艷萍;人巨細胞病毒UL136基因在臨床低傳代分離株中多態(tài)性分析[J];中華微生物學和免疫學雜志;2003年09期
3 齊瑩,盧穎,馬艷萍,阮強,何蓉,吉耀華,劉慶,陳淑榮;人巨細胞病毒UL138～142基因在臨床低傳代分離株中的多態(tài)性研究[J];中華微生物學和免疫學雜志;2004年03期
4 吉耀華,阮強,何蓉,齊瑩,馬艷萍,孫崢嶸,劉慶,陳淑榮,周艷麗;人巨細胞病毒UL149基因在臨床低傳代分離株中的多態(tài)性研究[J];中華微生物學和免疫學雜志;2004年12期
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