胞嘧啶脱氨酶APOBEC3F抗病毒调控机制的研究
发布时间：2019-03-21 18:17
【摘要】：APOBEC3F(A3F)与APOBEC3G(A3G)位于同一染色体上，且只有24667个碱基间隔，研究发现在表达A3G的结直肠恶性腺瘤、慢性粒细胞性白血病和上皮细胞内，也检测到了A3F的表达。他们的N端相似率可达到100%，A3F有7个外显子，A3G有8个外显子。A3F同样具有类似于A3G的抗病毒活性。流行病学调查分析，天然存在两种亚型A3F，不同点在于第231位的氨基酸残基,一种是缬氨酸(Valine,V)，另一种是异亮氨酸(Isoleucine,I)。 Vif(viral infectivity factor)蛋白是所有的慢病毒(除了马传染性贫血病毒，Equine infectious anemia virus)编码的一种病毒辅助蛋白。在HIV感染过程中，病毒的Vif蛋白与宿主细胞内的细胞因子Cul5，ElonginB和ElonginC形成泛素连接酶E3复合物，通过泛素化和蛋白酶降解途径，克服机体内的天然防御因子胞嘧啶脱氨酶APOBEC3家族蛋白的抗病毒活性。 在HIV-1Vif研究的基础上，本论文对人A3F蛋白对不同亚型的HIV病毒及逆转录转座子LINE-1的调控机制进行了研究。本论文证实，A3F的两种亚型均具有抑制病毒感染性的能力，且当Vif缺失时，抑制率可达80%左右。本论文还证实大部分亚型的HIV-1病毒的Vif蛋白对A3F的两种亚型降解能力几乎相同，只有3种亚型的Vif蛋白对A3F的两种亚型降解能力不同，原因可能是实验中的Vif蛋白虽然来源于不同亚型病毒，但是Vif上与人A3F蛋白的结合的功能区比较保守，，因此降解能力几乎相同。这为研究A3F蛋白的抗病毒能力及机制的提供理论依据，也将有助于研究A3F基因多态性与不同亚型病毒的分布之间的关系。
[Abstract]:APOBEC3F (A3F) and APOBEC3G (A3G) are located on the same chromosome with only 24667 BP spaced. A3F expression was also detected in malignant colorectal adenoma, chronic myeloid leukemia and epithelial cells expressing A3G. Their N-terminal similarity rate was 100%, A3F had 7 exons and A3G had 8 exons. A3F also had antiviral activity similar to A3G. Epidemiological analysis showed that there were two subtypes of A3F in nature, one was valine (Valine,V) and the other was isoleucine (Isoleucine,I), which was different from the amino acid residue at position 231. Vif (viral infectivity factor) proteins are all lentiviruses (except a viral helper protein encoded by equine infectious anemia virus, Equine infectious anemia virus). In the course of HIV infection, the Vif protein of the virus forms a ubiquitin ligase E3 complex with cytokines Cul5,ElonginB and ElonginC in the host cells. Overcome the antiviral activity of cytosine deaminase APOBEC3 family protein, a natural defense factor in the organism. Based on the study of HIV-1Vif, the regulatory mechanism of human A3F protein on different subtypes of HIV virus and retrotransposon LINE-1 was studied in this paper. This study confirmed that both subtypes of A3F have the ability to inhibit virus infection, and when Vif is absent, the inhibition rate can reach about 80%. This study also confirmed that the degradation ability of Vif protein of most subtypes of HIV-1 virus to A3F was almost the same, and only three subtypes of Vif protein had different degradation ability of two subtypes of A3F, and the degradation ability of the two subtypes of A3F was different between the two subtypes of A3F. The reason may be that although the Vif protein in the experiment comes from different subtypes of virus, the binding function of Vif to human A3F protein is conservative, so the ability of degradation is almost the same. This will provide theoretical basis for studying the anti-virus ability and mechanism of A3F protein, and will also be helpful to study the relationship between A3F gene polymorphism and the distribution of different subtypes of viruses.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.91
本文编号：2445195
[Abstract]:APOBEC3F (A3F) and APOBEC3G (A3G) are located on the same chromosome with only 24667 BP spaced. A3F expression was also detected in malignant colorectal adenoma, chronic myeloid leukemia and epithelial cells expressing A3G. Their N-terminal similarity rate was 100%, A3F had 7 exons and A3G had 8 exons. A3F also had antiviral activity similar to A3G. Epidemiological analysis showed that there were two subtypes of A3F in nature, one was valine (Valine,V) and the other was isoleucine (Isoleucine,I), which was different from the amino acid residue at position 231. Vif (viral infectivity factor) proteins are all lentiviruses (except a viral helper protein encoded by equine infectious anemia virus, Equine infectious anemia virus). In the course of HIV infection, the Vif protein of the virus forms a ubiquitin ligase E3 complex with cytokines Cul5,ElonginB and ElonginC in the host cells. Overcome the antiviral activity of cytosine deaminase APOBEC3 family protein, a natural defense factor in the organism. Based on the study of HIV-1Vif, the regulatory mechanism of human A3F protein on different subtypes of HIV virus and retrotransposon LINE-1 was studied in this paper. This study confirmed that both subtypes of A3F have the ability to inhibit virus infection, and when Vif is absent, the inhibition rate can reach about 80%. This study also confirmed that the degradation ability of Vif protein of most subtypes of HIV-1 virus to A3F was almost the same, and only three subtypes of Vif protein had different degradation ability of two subtypes of A3F, and the degradation ability of the two subtypes of A3F was different between the two subtypes of A3F. The reason may be that although the Vif protein in the experiment comes from different subtypes of virus, the binding function of Vif to human A3F protein is conservative, so the ability of degradation is almost the same. This will provide theoretical basis for studying the anti-virus ability and mechanism of A3F protein, and will also be helpful to study the relationship between A3F gene polymorphism and the distribution of different subtypes of viruses.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.91
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