本文選題：艾滋病病毒 + 前病毒DNA　； 參考：《中國(guó)疾病預(yù)防控制中心》2016年博士論文

【摘要】：研究目的和意義：HIV-1感染由于持續(xù)存在的病毒儲(chǔ)藏庫(kù)而難以治愈。在實(shí)現(xiàn)HIV-1治愈之前,最有效的治療方法仍然是高效抗逆轉(zhuǎn)錄病毒治療(Highly Active Antiretroviral Therapy, HAART)。2003年,我國(guó)開(kāi)始在全國(guó)范圍內(nèi)實(shí)行免費(fèi)的抗病毒治療,至2015年底累計(jì)47萬(wàn)余艾滋病患者接受了抗病毒治療。但是HIV-1的耐藥性是抗病毒治療過(guò)程中面臨的嚴(yán)重問(wèn)題。HIV-1以復(fù)雜的準(zhǔn)種形式存在,在不同種類(lèi)和強(qiáng)度的藥物選擇壓力下,處于動(dòng)態(tài)的變化過(guò)程。在HIV-1感染發(fā)展過(guò)程中,血漿中病毒變異會(huì)持續(xù)地進(jìn)入整合的前病毒中。目前,對(duì)于全血前病毒DNA與血漿病毒RNA耐藥準(zhǔn)種變異差異的研究較為有限。因此,本研究采用深度測(cè)序技術(shù)結(jié)合血漿病毒RNA和全血前病毒DNA分析兩者之間耐藥準(zhǔn)種的變異及其對(duì)長(zhǎng)期抗病毒治療結(jié)果的影響,并對(duì)吡啶酮化合物抗HIV-1活性進(jìn)行了研究。該研究將為HIV-1耐藥監(jiān)測(cè),優(yōu)化抗病毒治療策略及藥物的研發(fā)提供重要的科學(xué)依據(jù)。研究方法：1、本研究回顧性的納入我國(guó)河南、安徽地區(qū)長(zhǎng)期接受抗病毒治療的既往獻(xiàn)血HIV-1感染者為研究對(duì)象。初始治療方案為以3TC為主的后期一線(xiàn)治療藥物。共納入43例HIV-1感染者,根據(jù)一線(xiàn)治療方案的治療結(jié)果將其劃分為病毒抑制成功組(23人)和病毒抑制失敗組(20人)。2、以HIV-1 pol基因逆轉(zhuǎn)錄酶區(qū)為研究指標(biāo),利用深度測(cè)序方法獲得每例病人全血前病毒DNA和血漿病毒RNA的耐藥準(zhǔn)種序列并進(jìn)行比較。建立Taqman熒光定量PCR方法,對(duì)全血前病毒DNA進(jìn)行定量檢測(cè)。分析治療前耐藥準(zhǔn)種與長(zhǎng)期抗病毒治療結(jié)果的相關(guān)性。3、利用CorMut軟件和Bayesian網(wǎng)絡(luò)分析全血前病毒DNA和血漿病毒RNA準(zhǔn)種中的治療失敗相關(guān)特征性位點(diǎn),并以此特征性位點(diǎn)和治療結(jié)果為變量分析與治療失敗直接相關(guān)的突變位點(diǎn),并進(jìn)一步分析其在長(zhǎng)期抗病毒治療過(guò)程中的動(dòng)態(tài)變化。4、利用基于TZM-bl細(xì)胞系的HIV-1病毒表型耐藥性檢測(cè)方法,對(duì)不同的吡啶酮化合物抗HIV-1的活性,特別是抗HIV-1耐藥株的活性進(jìn)行研究。研究結(jié)果：1、基于深度測(cè)序技術(shù)的前病毒DNA和血漿病毒RNA耐藥準(zhǔn)種變異的比較本研究通過(guò)深度測(cè)序技術(shù)獲得43例HIV-1感染者感染前后不同時(shí)間點(diǎn)共66份樣本的血漿病毒RNA和全血前病毒DNA的pol基因逆轉(zhuǎn)錄酶區(qū)序列。37份樣本中檢測(cè)到耐藥位點(diǎn),其中67.57%(25/37)的樣本中檢測(cè)到劣勢(shì)耐藥位點(diǎn)。不論在血漿RNA還是前病毒DNA,耐藥位點(diǎn)K103N和Y181C均具有較高的發(fā)生頻率。血漿RNA和前病毒DNA中的耐藥位點(diǎn)和頻率存在差異。優(yōu)勢(shì)耐藥位點(diǎn)出現(xiàn)的M41L、M184I、 E138A、G190E和M230I僅在全血DNA中檢測(cè)到。在劣勢(shì)耐藥位點(diǎn)中出現(xiàn)的M184V/I、 T215I、K219R、E138K、H22IY和M2301僅在全血DNA中檢測(cè)到。在進(jìn)行藥物敏感性分析時(shí),分析優(yōu)勢(shì)耐藥位點(diǎn)時(shí),有32.43%(12/37)樣本的血漿RNA和前病毒DNA呈現(xiàn)出對(duì)一線(xiàn)治療藥物不同程度的耐受,其中33.33%(4/12)樣本的前病毒DNA對(duì)一線(xiàn)治療藥物的耐受高于血漿病毒RNA。分析劣勢(shì)耐藥位點(diǎn)時(shí),發(fā)現(xiàn)有62.16%(23/37)樣本的血漿RNA和前病毒DNA呈現(xiàn)出對(duì)一線(xiàn)治療藥物不同程度的耐受,其中69.57%(16/23)樣本的前病毒DNA對(duì)一線(xiàn)治療藥物的耐受程度高于血漿病毒RNA。2、治療前耐藥準(zhǔn)種與長(zhǎng)期抗病毒治療結(jié)果相關(guān)性分析治療前HIV-1感染者全血前病毒DNA載量與血漿病毒載量(viral load, VL)呈顯著的正相關(guān)關(guān)系(p=0.003)。治療失敗的15例HIV-1感染者在治療過(guò)程中HIV-1DNA載量的動(dòng)態(tài)變化與血漿RNA VL呈現(xiàn)相同的變化趨勢(shì)。將治療前血漿病毒RNA和全血前病毒DNA中優(yōu)勢(shì)耐藥位點(diǎn)和劣勢(shì)耐藥位點(diǎn)統(tǒng)稱(chēng)為治療前耐藥(RNADNA)。利用logistic回歸分析與長(zhǎng)期抗病毒治療結(jié)果相關(guān)的基線(xiàn)臨床特征。納入變量包括CD4+T細(xì)胞數(shù),血漿VL,前病毒DNA載量,治療前有無(wú)耐藥(RNADNA),治療前RNA中有無(wú)耐藥,治療前DNA有無(wú)耐藥。結(jié)果顯示在多因素logistic回歸中,治療前有無(wú)耐藥(RNADNA)是與抗病毒治療失敗相關(guān)的變量[OR=5.9(95%CI 1.4-24.7),p=0.01]。進(jìn)一步分析發(fā)現(xiàn),當(dāng)血漿病毒RNA耐藥位點(diǎn)的頻率增加1%時(shí),病毒抑制失敗率增加了1.3%。3、HIV-1 pol基因逆轉(zhuǎn)錄酶區(qū)治療失敗直接相關(guān)位點(diǎn)分析治療前,血漿病毒RNA中治療失敗直接相關(guān)位點(diǎn)包括非核苷類(lèi)耐藥位點(diǎn)K101E、K103N、E138K和V179D,以及多態(tài)性位點(diǎn)K64R、K102Q、V111I、D123N、I135T、 S162Y、E169D、Q174K、I202V、R211G、R211T、R211M、S251C。全血前病毒DNA中治療失敗直接相關(guān)位點(diǎn)包括非核苷類(lèi)耐藥位點(diǎn)G190A和V179D,以及多態(tài)性位點(diǎn)E42K、K64R、K102Q、D123N、R125K、Q174K、V189I、R211T、R211M、R211Q、 V245E、D250N。在治療過(guò)程中,血漿病毒RNA中新出現(xiàn)的治療失敗直接相關(guān)位點(diǎn)包括非核苷類(lèi)耐藥位點(diǎn)K103S、H221Y、Y181C,核苷類(lèi)耐藥位點(diǎn)M184V,以及多態(tài)性位點(diǎn)I31L、K32R、V35I、T39A、K173R、I178M、Q197E和E203D。全血前病毒DNA中新出現(xiàn)的治療失敗相關(guān)位點(diǎn)包括非核苷類(lèi)耐藥位點(diǎn)K103S、V179I、G190E,核苷類(lèi)耐藥位點(diǎn)D67N、M184V和M184I,以及多態(tài)性位點(diǎn)K32R、V35I、T39A和G51R。經(jīng)分析發(fā)現(xiàn),在長(zhǎng)期治療過(guò)程中,治療失敗直接相關(guān)位點(diǎn)包括耐藥位點(diǎn)K103N、Y181C,和多態(tài)性位點(diǎn)K102Q、E169D、R211G、I202V、R211T、V245E以較高頻率存在。4、吡啶酮化合物抗HIV-1活性的研究由于在血漿RNA和前病毒DNA中,耐藥位點(diǎn)K103N和Y181C均具有較高的發(fā)生頻率,為此,我們和北京大學(xué)藥學(xué)院合作設(shè)計(jì)合成一類(lèi)NNRTIs,即吡啶酮化合物3-碘-4-(2-環(huán)己基甲基氧)-6-苯乙基-2(2H)-吡啶酮的5種構(gòu)象化合物7-cis、7-mix、 7-trans、7-trans-1、7-trans-2,對(duì)其抗HIV-1耐藥株的活性進(jìn)行了檢測(cè)。結(jié)果顯示,該5種化合物對(duì)TZM-bl細(xì)胞均具有較低的毒性,對(duì)HIV-1 SF33雙嗜性實(shí)驗(yàn)室標(biāo)準(zhǔn)株和HIV-1 A17非核苷類(lèi)逆轉(zhuǎn)錄酶耐藥的標(biāo)準(zhǔn)株具有較好的抑制活性,EC50分別為0.003-0.503州和0.117-19.657μM,治療指數(shù)分別為在323-100000和8.2-2564之間。其中化合物7-mix、7-trans、7-trans-1、7-trans-2對(duì)我國(guó)臨床分離HIV-I流行株CRF07_BC(XJDC6371, XJDC6291和CBJB256)、CRF01_AE(BJM543)、B'(020100968和020100096)3種亞型毒株均有不同程度抑制活性(EC50:0.4-90nM)。其中7-trans-2化合物能夠顯著的抑制實(shí)驗(yàn)室適應(yīng)株和攜帶K103N和Y181C耐藥突變的耐藥株HIV-1 A17, EC50分別為3 nM和117 nM(SI2500),對(duì)所有的臨床毒株的EC50值為0.4-57 nM,SI為5263-750000。結(jié)論：本研究從血漿RNA和全血前病毒DNA方面研究了HIV-1準(zhǔn)種變異對(duì)長(zhǎng)期抗病毒治療結(jié)果的影響。深度測(cè)序揭示了全血前病毒DNA和血漿病毒RNA具有不同的耐藥準(zhǔn)種。治療前血漿病毒RNA和前病毒DNA耐藥準(zhǔn)種的存在將會(huì)導(dǎo)致抗病毒治療的失敗,血漿病毒RNA耐藥位點(diǎn)的頻率升高會(huì)增加抗病毒治療失敗的風(fēng)險(xiǎn)�；谏疃葴y(cè)序技術(shù)的血漿RNA和前病毒DNA的耐藥檢測(cè)應(yīng)該考慮應(yīng)用于HIV-1耐藥監(jiān)測(cè)。吡啶酮化合物對(duì)攜帶K103N和Y181C的HIV-I耐藥株具有一定的抑制活性,同時(shí)對(duì)我國(guó)HIV-I主要流行株也具有廣泛的抑制作用。本研究對(duì)于耐藥監(jiān)測(cè)的指導(dǎo)和藥物的研發(fā)具有重要的意義。
[Abstract]:The purpose and significance of the study: HIV-1 infection is difficult to cure because of the persistent virus storage. Before the HIV-1 cure, the most effective treatment is the Highly Active Antiretroviral Therapy (HAART).2003 year, and our country begins to carry out free antiviral treatment throughout the country to 2015 More than 47 million AIDS patients received antiviral therapy at the end of the year. But HIV-1 resistance is a serious problem in the process of antiviral treatment,.HIV-1 is in a complex quasi species, under the pressure of different types and intensity of drug selection, in the dynamic process of change. In the development of HIV-1 infection, the virus variation in plasma will be in the process of development of HIV-1 infection Continuing to enter the integrated pre virus. Currently, there is limited study on the difference between pre - blood virus DNA and plasma virus RNA - resistant quasi species variation. Therefore, this study uses deep sequencing technology combined with plasma virus RNA and pre - blood virus DNA analysis of the variation of drug resistance quasi species and their effects on long-term antiviral treatment results, The anti HIV-1 activity of pyridone compound is studied. This study will provide an important scientific basis for HIV-1 resistance monitoring, optimization of antiviral therapy strategies and drug development. 1. This study was reviewed in Henan, China, and in the Anhui region, who had been treated for a long time in the blood donation of HIV-1. 43 cases of HIV-1 infection were included in the initial treatment program, which was mainly 3TC in the late first line treatment. According to the treatment results of the first line treatment, they were divided into virus inhibition group (23 people) and virus inhibition failure group (20 people).2, and HIV-1 pol gene reverse transcriptase region was used as the study index, and each case was obtained by deep sequencing method. The sequence and comparison of the drug resistance quasispecies of human pre blood virus DNA and plasma virus RNA were compared. The Taqman fluorescence quantitative PCR method was established for quantitative detection of the pre blood virus DNA. The correlation between the pre treatment and the long-term antiviral treatment results was analyzed, and the CorMut software and Bayesian network were used to analyze the pre whole blood virus DNA and the plasma virus RNA. The treatment failure related characteristic loci in the quasi species, and the characteristic loci and the therapeutic results as variables, analyze the mutation sites that are directly related to the treatment failure, and further analyze the dynamic changes in the long-term antiviral therapy,.4, using the TZM-bl cell line based HIV-1 virus phenotype resistance detection method, to different pyridoidin. The anti HIV-1 activity of acetone compounds, especially the activity of anti HIV-1 resistant strains. 1, comparison of pre virus DNA and plasma virus RNA resistant quasi species variation based on deep sequencing technology, this study was used to obtain the plasma virus RNA of 66 samples in 43 cases of HIV-1 infected persons at different time points in different time points by deep sequencing technology. The resistance loci were detected in.37 samples from the pol gene reverse transcriptase sequence of the pre blood virus DNA, of which 67.57% (25/37) samples were detected at the disadvantaged loci. Both the plasma RNA and the pre viral DNA, the resistance loci K103N and Y181C have high frequency. The drug resistance loci and frequencies in the plasma RNA and the virus DNA are found. M41L, M184I, E138A, G190E and M230I were detected only in the whole blood DNA. M184V/I, T215I, K219R, E138K, H22IY, and M2301 were detected only in the whole blood. In the analysis of drug sensitivity, the analysis of the dominant loci was 32.43% Virus DNA showed tolerance to a different degree of first-line treatment, of which 33.33% (4/12) samples were tolerant to first-line therapy than in plasma viral RNA. analysis at inferior resistance sites, and 62.16% (23/37) samples of plasma RNA and pre viral DNA showed tolerance to different levels of first-line treatment, of which 69.57% (16/23) the tolerance of the pre viral DNA to the first-line treatment is higher than that of the plasma virus RNA.2. The correlation between the pre treatment drug resistance quasi species and the long-term antiviral treatment results is a significant positive correlation between the DNA load of the pre blood virus DNA and the plasma viral load (viral load, VL) before the treatment of HIV-1 infection (p=0.003). 15 cases of the failure of the treatment of HIV- The dynamic changes of the HIV-1DNA load and the plasma RNA VL were the same trend during the treatment process. The pretreatment plasma virus RNA and the predominant virus DNA were called pretreatment resistance (RNADNA), and the baseline associated with the long-term antiviral treatment was associated with the logistic regression analysis. The variables included the number of CD4+T cells, the plasma VL, the DNA load of the pre virus, the drug resistance (RNADNA) before treatment, the drug resistance in RNA before treatment, and the resistance to DNA before treatment. The results showed that in the multiple factor Logistic regression, no drug resistance (RNADNA) was a variable (95%CI 1.4-24.7) that was associated with the failure of antiviral therapy (95%CI 1.4-24.7) before treatment. Further analysis showed that when the frequency of the RNA resistance loci of the plasma virus increased by 1%, the failure rate of virus inhibition increased by 1.3%.3. Before the direct correlation site analysis of the HIV-1 pol gene reverse transcriptase region treatment failure, the direct related loci of the treatment failure in the plasma virus RNA include the non nucleoside resistance loci K101E, K103N, E138K and V179D, and more. K64R, K102Q, V111I, D123N, I135T, S162Y, E169D, Q174K, I202V, R211G, R211T, R211M, including non nucleoside resistant loci and polymorphic loci K103S, H221Y, Y181C, nucleoside resistance loci, M184V, and polymorphic loci I31L, K32R, V35I, T39A, K173R, and I178M, including non nucleoside resistance loci, including non nucleoside resistance loci, are the direct related sites of the new treatment failure in the plasma virus RNA 190E, nucleoside resistant sites D67N, M184V and M184I, and polymorphic loci K32R, V35I, T39A and G51R. have been found that the direct related sites of treatment failure include K103N, Y181C, and polymorphic loci in the long-term treatment process. Because of the high frequency of drug resistance loci K103N and Y181C in plasma RNA and DNA, we collaborated with the Peking University Institute of pharmacy to design and synthesize a class of NNRTIs, namely, the 5 conformation compounds of the pyridone compound 3- iodide -4- (2- cyclohexyl methyl oxygen) -6- phenyl ethyl -2 (2H) pyridone. -1,7-trans-2, the activity of its anti HIV-1 resistant strain was detected. The results showed that the 5 compounds had low toxicity to TZM-bl cells. The standard strain of HIV-1 SF33 double tropic laboratory standard strain and HIV-1 A17 non nucleoside reverse transcriptase resistant standard strain had better inhibitory activity, EC50 was 0.003-0.503 state and 0.117-19.657 mu M, respectively. The index of treatment was between 323-100000 and 8.2-2564. Compounds 7-mix, 7-trans, and 7-trans-1,7-trans-2 had different degrees of inhibitory activity to 3 subtypes of HIV-I epidemic strains, CRF07_BC (XJDC6371, XJDC6291 and CBJB256), CRF01_AE (BJM543), and B'(020100968 and 020100096). The substance can significantly inhibit the laboratory adaptation strain and the drug resistant strain HIV-1 A17 carrying K103N and Y181C resistance mutations, EC50 is 3 nM and 117 nM (SI2500), and the EC50 value of all clinical isolates is 0.4-57 nM. The effect of treatment results. Deep sequencing revealed that the pre - blood virus DNA and the plasma virus RNA have different drug resistance para. The presence of pre - treatment plasma viral RNA and the pre - viral DNA resistance quasispecies will lead to the failure of antiviral therapy. The increase in the frequency of the drug resistance site of the plasma virus RNA will increase the risk of the failure of the antiviral therapy. The resistance detection of plasma RNA and previral DNA by sequencing technology should be considered for HIV-1 resistance monitoring. Pyridone compounds have a certain inhibitory activity for the HIV-I resistant strains carrying K103N and Y181C, and also have extensive inhibitory effects on the major HIV-I strains in China. The guidance of drug resistance monitoring and drug development in this study It is of great significance.
【學(xué)位授予單位】：中國(guó)疾病預(yù)防控制中心
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R512.91

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6 郭義,張艷軍,徐湯萍,鮑家鑄;手十二井穴刺絡(luò)放血對(duì)腦缺血大鼠缺血區(qū)組織Na~＋、K~＋影響的動(dòng)態(tài)觀察[J];甘肅中醫(yī)學(xué)院學(xué)報(bào);1996年04期

7 常英姿;Na~＋─H~＋交換與血管平滑肌細(xì)胞增殖[J];國(guó)外醫(yī)學(xué)(生理、病理科學(xué)與臨床分冊(cè));1996年04期

8 房曉yN;Na~+/H~+交換體與血管平滑肌細(xì)胞增殖[J];心臟雜志;2004年02期

9 鐘銘英;;一種多特異性單克隆抗DNA自身抗體亦與細(xì)胞表面蛋白結(jié)合[J];國(guó)外醫(yī)學(xué).皮膚病學(xué)分冊(cè);1988年02期

10 楊美香;Na~+/H~+交換子在腫瘤研究中的價(jià)值[J];國(guó)外醫(yī)學(xué)(免疫學(xué)分冊(cè));2004年01期

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8 焦麗燕;血漿RNA和PBMCs DNA HIV-1耐藥準(zhǔn)種多態(tài)性和分子進(jìn)化研究[D];中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院;2011年

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4 劉晨;Na在荒漠植物霸王響應(yīng)干旱中的元素特征研究[D];蘭州大學(xué);2012年

5 姚磊;日糧營(yíng)養(yǎng)水平對(duì)山羊前胃上皮Na~+/H~+交換蛋白及氨轉(zhuǎn)運(yùn)蛋白表達(dá)的影響[D];南京農(nóng)業(yè)大學(xué);2014年

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7 楊洪兵;小麥拒Na～+機(jī)理的研究[D];山東師范大學(xué);2001年

8 郭慶水;木欖Na~+/H~+逆向運(yùn)輸?shù)鞍谆虻目寺D];海南大學(xué);2010年

9 馬淑杰;Na~+對(duì)干旱脅迫下棉花生長(zhǎng)及適應(yīng)性的調(diào)節(jié)作用[D];魯東大學(xué);2015年

10 滕新霞;水稻液泡膜Na~+/H~+逆向轉(zhuǎn)運(yùn)蛋白基因OsNHX2的功能分析[D];南京農(nóng)業(yè)大學(xué);2008年

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