人类抗病毒因子A3G与A3F的研究

发布时间：2018-04-10 16:10

本文选题：APOBEC3G/A3G + APOBEC3F/A3F　；参考：《电子科技大学》2006年硕士论文

【摘要】： Vif(viral infectivity factor)是HIV-1自身编码的附属蛋白之一,在HIV-1复制过程中起着重要作用。最近,对Vif的研究揭示了固有免疫的新成员—APOBEC3G、APOBEC3F,是一种抑制HIV-1感染的细胞内蛋白,也是一种胞苷脱氨酶,在病毒复制末期被整合进子代病毒粒子,继而引发逆转录病毒cDNA负链产生大量的dC-dU突变,能致死性突变反转录病毒和反转录元件。研究发现,APOBEC3G和APOBEC3F为APOBEC家族成员,位于人类染色体22q12-q13,二者均能介导固有免疫,对病毒尤其是对逆转录病毒具广谱抗病毒效应,其中,APOBEC3G对HBV具有强烈的抑制作用,国外肿瘤实验表明,APOBEC3G抑制MLV效果显著,抑制HBV复制明显优于抗病毒药物3TC,并可使对照中的HBV DNA至少下降50倍。与APOBEC3G一样,APOBEC3F也具有DNA编辑功能,可与APOBEC3G共表达,一起抵抗病毒侵入。新近研究发现,APOBEC3G和APOBEC3F为人体细胞表达的两种胞苷脱氨酶,二者对病毒表达的Vif均存在重要拮抗关系。Vif是HIV自身基因组vif基因表达的一种重要病毒感染因子,与病毒感染密切相关。机体APOBEC3G和APOBEC3F过量表达,可有效抵抗病毒Vif的功能行使,此一现象对Vif缺陷株病毒(?Vif)失去感染性尤为显著。APOBEC3G、APOBEC3F与HIV病毒Vif之间存在的这一拮抗关系为艾滋病(acquired immune deficiency syndrome, AIDS)治疗带来了新的希望和曙光。以APOBEC3G和APOBEC3F作新药靶点,研究开发相关蛋白药物或生物制剂,对于艾滋病及其它逆转录病毒病防治无疑具有非常重要的意义。目前,从生物信息学角度研究分析APOBEC3G和APOBEC3F基因的文献不多,国内除王翌等对APOBEC3G基因曾作过一些粗略分析外,APOBEC3F基因研究文献鲜见报道。本研究在开展对APOBEC3F基因生物信息学研究的同时,结合分子生物学实验尝试APOBEC3G基因提取和分析,以期从生物信息学和分子生物学角度揭示和阐述APOBEC3G、APOBEC3F与病毒Vif之间的相互作用关系。在APOBEC3F基因生物信息学分析中,作者在基因水平分析了APOBEC3F基因特性;在蛋白质水平对其二级结构、卷曲螺旋以及细胞定位等进行了预测;运用基因库大量EST序列,通过电子克隆获得了猪APOBEC3F的全基因序列,并进行了相关
[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.
【学位授予单位】：电子科技大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

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