本文選題：APOBEC3G/A3G + APOBEC3F/A3F�。� 參考：《電子科技大學(xué)》2006年碩士論文

【摘要】： Vif(viral infectivity factor)是HIV-1自身編碼的附屬蛋白之一,在HIV-1復(fù)制過程中起著重要作用。最近,對Vif的研究揭示了固有免疫的新成員—APOBEC3G、APOBEC3F,是一種抑制HIV-1感染的細(xì)胞內(nèi)蛋白,也是一種胞苷脫氨酶,在病毒復(fù)制末期被整合進(jìn)子代病毒粒子,繼而引發(fā)逆轉(zhuǎn)錄病毒cDNA負(fù)鏈產(chǎn)生大量的dC-dU突變,能致死性突變反轉(zhuǎn)錄病毒和反轉(zhuǎn)錄元件。 研究發(fā)現(xiàn),APOBEC3G和APOBEC3F為APOBEC家族成員,位于人類染色體22q12-q13,二者均能介導(dǎo)固有免疫,對病毒尤其是對逆轉(zhuǎn)錄病毒具廣譜抗病毒效應(yīng),其中,APOBEC3G對HBV具有強烈的抑制作用,國外腫瘤實驗表明,APOBEC3G抑制MLV效果顯著,抑制HBV復(fù)制明顯優(yōu)于抗病毒藥物3TC,并可使對照中的HBV DNA至少下降50倍。與APOBEC3G一樣,APOBEC3F也具有DNA編輯功能,可與APOBEC3G共表達(dá),一起抵抗病毒侵入。新近研究發(fā)現(xiàn),APOBEC3G和APOBEC3F為人體細(xì)胞表達(dá)的兩種胞苷脫氨酶,二者對病毒表達(dá)的Vif均存在重要拮抗關(guān)系。Vif是HIV自身基因組vif基因表達(dá)的一種重要病毒感染因子,與病毒感染密切相關(guān)。機體APOBEC3G和APOBEC3F過量表達(dá),可有效抵抗病毒Vif的功能行使,此一現(xiàn)象對Vif缺陷株病毒(?Vif)失去感染性尤為顯著。APOBEC3G、APOBEC3F與HIV病毒Vif之間存在的這一拮抗關(guān)系為艾滋病(acquired immune deficiency syndrome, AIDS)治療帶來了新的希望和曙光。以APOBEC3G和APOBEC3F作新藥靶點,研究開發(fā)相關(guān)蛋白藥物或生物制劑,對于艾滋病及其它逆轉(zhuǎn)錄病毒病防治無疑具有非常重要的意義。 目前,從生物信息學(xué)角度研究分析APOBEC3G和APOBEC3F基因的文獻(xiàn)不多,國內(nèi)除王翌等對APOBEC3G基因曾作過一些粗略分析外,APOBEC3F基因研究文獻(xiàn)鮮見報道。本研究在開展對APOBEC3F基因生物信息學(xué)研究的同時,結(jié)合分子生物學(xué)實驗嘗試APOBEC3G基因提取和分析,以期從生物信息學(xué)和分子生物學(xué)角度揭示和闡述APOBEC3G、APOBEC3F與病毒Vif之間的相互作用關(guān)系。在APOBEC3F基因生物信息學(xué)分析中,作者在基因水平分析了APOBEC3F基因特性;在蛋白質(zhì)水平對其二級結(jié)構(gòu)、卷曲螺旋以及細(xì)胞定位等進(jìn)行了預(yù)測;運用基因庫大量EST序列,通過電子克隆獲得了豬APOBEC3F的全基因序列,并進(jìn)行了相關(guān)
[Abstract]:Vif(viral infectivity factor is one of the accessory proteins encoded by HIV-1 itself and plays an important role in the process of HIV-1 replication.Recent studies of Vif have revealed that a new member of innate immunity, -APOBEC3G, an intracellular protein that inhibits HIV-1 infection, is also a cytidine deaminase that is integrated into offspring virus particles at the end of viral replication.In turn, a large number of dC-dU mutations are produced in the negative strand of retrovirus cDNA, which can cause fatal mutation of retrovirus and retrovirus elements.It was found that APOBEC3G and APOBEC3F are members of the APOBEC family, located on human chromosome 22q12-q13. Both of them can mediate innate immunity and have broad-spectrum antiviral effects on viruses, especially on retroviruses, among which APOBEC3G has a strong inhibitory effect on HBV.Foreign tumor experiments showed that APOBEC3G had a significant effect on inhibiting MLV and inhibiting HBV replication, which was better than that of antiviral drug 3TC.The HBV DNA in the control group was reduced by at least 50 times.Like APOBEC3G, APOBEC3F also has DNA editing function, which can be co-expressed with APOBEC3G to resist virus invasion.It has been recently found that APOBEC3G and APOBEC3F are two cytidine deaminases expressed in human cells. Both of them have an important antagonistic relationship to the Vif expressed by the virus. Vif is an important viral infection factor for the expression of vif gene in the HIV genome.It is closely related to virus infection.Overexpression of APOBEC3G and APOBEC3F can effectively resist the function of viral Vif.The antagonistic relationship between APOBEC3G, APOBEC3G, APOBEC3F and HIV virus Vif brings new hope and dawn to the treatment of Vif acquired immune deficiency syndrome (AIDSs).Using APOBEC3G and APOBEC3F as the targets of new drugs, the research and development of related protein drugs or biological agents is undoubtedly of great significance for the prevention and treatment of AIDS and other retrovirals.At present, there are few literatures on the analysis of APOBEC3G and APOBEC3F genes from the point of view of bioinformatics, and there are few reports on the studies of APOBEC3G genes in China except Wang Yi.In the bioinformatics analysis of APOBEC3F gene, the author analyzed the characteristics of APOBEC3F gene at the gene level, predicted its secondary structure, crimp helix and cellular location at the protein level, and used a large number of EST sequences in the gene bank.The whole gene sequence of porcine APOBEC3F was obtained by electronic cloning.
【學(xué)位授予單位】：電子科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2006
【分類號】：R392

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本文編號：1731942