胞嘧啶脫氨酶APOBEC3F抗病毒調(diào)控機(jī)制的研究
發(fā)布時(shí)間：2019-03-21 18:17
【摘要】：APOBEC3F(A3F)與APOBEC3G(A3G)位于同一染色體上，且只有24667個堿基間隔，研究發(fā)現(xiàn)在表達(dá)A3G的結(jié)直腸惡性腺瘤、慢性粒細(xì)胞性白血病和上皮細(xì)胞內(nèi)，也檢測到了A3F的表達(dá)。他們的N端相似率可達(dá)到100%，A3F有7個外顯子，A3G有8個外顯子。A3F同樣具有類似于A3G的抗病毒活性。流行病學(xué)調(diào)查分析，天然存在兩種亞型A3F，不同點(diǎn)在于第231位的氨基酸殘基,一種是纈氨酸(Valine,V)，另一種是異亮氨酸(Isoleucine,I)。 Vif(viral infectivity factor)蛋白是所有的慢病毒(除了馬傳染性貧血病毒，Equine infectious anemia virus)編碼的一種病毒輔助蛋白。在HIV感染過程中，病毒的Vif蛋白與宿主細(xì)胞內(nèi)的細(xì)胞因子Cul5，ElonginB和ElonginC形成泛素連接酶E3復(fù)合物，通過泛素化和蛋白酶降解途徑，克服機(jī)體內(nèi)的天然防御因子胞嘧啶脫氨酶APOBEC3家族蛋白的抗病毒活性。 在HIV-1Vif研究的基礎(chǔ)上，本論文對人A3F蛋白對不同亞型的HIV病毒及逆轉(zhuǎn)錄轉(zhuǎn)座子LINE-1的調(diào)控機(jī)制進(jìn)行了研究。本論文證實(shí)，A3F的兩種亞型均具有抑制病毒感染性的能力，且當(dāng)Vif缺失時(shí)，抑制率可達(dá)80%左右。本論文還證實(shí)大部分亞型的HIV-1病毒的Vif蛋白對A3F的兩種亞型降解能力幾乎相同，只有3種亞型的Vif蛋白對A3F的兩種亞型降解能力不同，原因可能是實(shí)驗(yàn)中的Vif蛋白雖然來源于不同亞型病毒，但是Vif上與人A3F蛋白的結(jié)合的功能區(qū)比較保守，，因此降解能力幾乎相同。這為研究A3F蛋白的抗病毒能力及機(jī)制的提供理論依據(jù)，也將有助于研究A3F基因多態(tài)性與不同亞型病毒的分布之間的關(guān)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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R512.91
本文編號：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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R512.91
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相關(guān)期刊論文 前3條
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3 Courtney PROCHNOW;Ronda BRANSTEITTER;;APOBEC deaminases-mutases with defensive roles for immunity[J];Science in China(Series C:Life Sciences);2009年10期
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