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系統識別號 U0026-3010201210243700
論文名稱(中文) 病毒偵測的先導型研究
論文名稱(英文) A pilot study of virus detection methods
校院名稱 成功大學
系所名稱(中) 分子醫學研究所
系所名稱(英) Institute of Molecular Medicine
學年度 101
學期 1
出版年 101
研究生(中文) 凌偉碩
研究生(英文) Wei-Shuo Ling
學號 t16991096
學位類別 碩士
語文別 中文
論文頁數 92頁
口試委員 指導教授-王憲威
召集委員-鄧景浩
口試委員-柯文謙
口試委員-柯乃熒
中文關鍵字 人類免疫缺失病毒  後天性免疫不全症候群  核酸篩檢方法  自動核酸擴增 
英文關鍵字 Human immunodeficiency virus (HIV)  acquired immunodeficiency syndrome (AIDS)  nucleic acid testing (NAT)  autocycling amplification 
學科別分類
中文摘要 後天性免疫不全症候群(AIDS;acquired immunodeficiency syndrome),於西元1981年發現首例病例,且截至西元2010年為止,全球約有三千四百萬人正感染愛滋病病毒。對於病患之投藥、治療時程甚至於此疾病之監控,皆取決於是否能夠精準地檢測感染以及監控病患體內之病毒數。近年來,以愛滋病病毒之核酸為偵測目標的檢測方式(NAT;nucleic acid testing)逐漸發展成熟,諸如反轉錄聚合酶鏈鎖反應(RT-PCR;reverse transcription polymerase chain reaction)、標的核酸序列擴增法(NASBA;nucleic acid sequence based amplification)等,因此我們希望研發一套以自動核酸擴增技術為基礎的高靈敏性檢測套組,並針對台灣分佈比例最高之B亞型愛滋病病毒其gag基因進行檢測。在本篇研究中,我們嘗試以兩種(X與Y型)自動核酸擴增檢測法針對愛滋病病毒標準質體(pHXB2)進行靈敏性、專一性等可行性測試。實驗結果顯示Y型自動核酸擴增檢測法對於快速以及準確地檢測HIV具有其許多優勢。首先,此檢測方法之靈敏度相當地高,目前已可以偵測到10個分子的HIV DNA 質體,且可於加熱後之血液中偵測到1個感染之T細胞。其次,此檢測方法非常省時且價廉,因為不需要經由抽取HIV RNA以及反轉錄等步驟,可以直接偵測HIV DNA,大幅降低額外反應所衍生之影響以及檢測所需之時間。再者,此檢測方法之專一性亦相當地高,因為只有當目標序列存在時,擴增反應才會進行。最後,偵測結果之判讀相當地簡便,因為有別於以往傳統膠體電泳分析方法,可以於反應最終產物中直接加入核酸染劑,即可以肉眼或紫外光影像系統直接觀察。綜觀本篇研究實驗結果,本檢測套組有相當大的潛力可以成為一套快速、價廉以及高精準度之HIV檢測套組。另外,透過設計、整合更多的專一性引子對,可以促使此檢測套組在臨床醫學亦或是商業套組中,對於全世界各種HIV基因型患者之檢測以及篩選提供更大的應用。
英文摘要 Human immunodeficiency virus (HIV) has resulted in more than 25 million deaths worldwide since its discovery. Currently, approximately 34 million people are living with AIDS (UNAIDS, 2011 Global Report). To effectively track the disease, tools developed for highly sensitive HIV detection that are rapid, cost-friendly, and static of accuracy in diagnosing HIV early infection and screening of clinical/donor specimens are necessary. In this study, we developed two autocycling amplification-based detection methods (X and Y types) for detecting HIV-1 B subtype virus that is predominantly circulating in Taiwan region (42.2%). The results showed that the Y-type autocycling amplification based assay possess many advantages for fast and accurate detection of HIV infection. First, this detection assay is sensitive because it can stably detect at least 10 copies of HIV nucleic acids and 1 infected Jurkat T reporter cell in boiled human blood. Second, the detection assay is time and cost effective because it can detect HIV DNA without complicated procedures such as extraction and reverse transcription of HIV RNA. Third, the detection is specific because it can amplify signals only when target sequences exist. Fourth, the interpretation of HIV positive/negative result does not require sophisticated tool because DNA staining dye can be simply added in the reaction product to distinguish amplified products by naked eyes or with UV light imaging system. Our data collectively indicated that the Y-type detection method has great potential to be a rapid, cost effective, and highly sensitive HIV detection kit. By designing and integrating more specific primers, the assay may have better clinical usage and commercial application in detecting and screening different HIV genotypes in HIV-1 infected specimens around the world.
論文目次 考試合格證明....................................................................................................................... I
中文摘要.............................................................................................................................. II
英文摘要.............................................................................................................................III
致謝.......................................................................................................................................V
目錄.....................................................................................................................................VI
表目錄...................................................................................................................................X
圖目錄.................................................................................................................................XI
附錄...................................................................................................................................XII
符號及縮寫......................................................................................................................XIII
緒論........................................................................................................................................1
一. 研究動機................................................................................................................1
二. 現行偵測方式以及其改善目標............................................................................3
1. RT-PCR technology...........................................................................................4
2. NASBA technology............................................................................................4
3. bDNA technology...............................................................................................4
三. X型扣鎖探針的原理與應用................................................................................6
1. 單核酸多型性分析與原位雜合........................................................................8
2. 微矩陣與多重檢測............................................................................................9
3. RNA分析.........................................................................................................10
4. 感染性致病源的檢測......................................................................................10
四. Y型恆溫套環式核酸擴增反應的原理與應用..................................................12
1. Bst DNA polymerase........................................................................................13
2. 引子對數目......................................................................................................13
3. 作用溫度..........................................................................................................13
五. 實驗目標..............................................................................................................16
實驗材料與方法..................................................................................................................17
一. 愛滋病病毒核酸序列資料收集與比對..............................................................17
二. 辨識目標序列挑選以及PLP扣鎖探針設計.....................................................17
三. 辨識目標序列挑選以及LAMP引子對設計.....................................................18
四. 磷酸激酶反應......................................................................................................19
五. X型扣鎖探針最佳使用量調整.............. ...........................................................19
六. X型扣鎖探針檢測..............................................................................................20
1. 黏合反應 (ligation) ........................................................................................20
(1) T4 DNA ligase中溫黏合反應................................................................20
(2) Ampligase DNA ligase循環溫度黏合反應...........................................21
(3) Taq DNA ligase循環溫度黏合反應......................................................22
2. 外切酶反應 (Exonuclease reaction) ..............................................................22
3. 滾式環形擴增反應 (RCA;rolling circle amplification) .............................23
七. Y型恆溫套環式核酸擴增反應..........................................................................23
1. 評估反應適用溫度..........................................................................................25
2. 測試反應作用時間..........................................................................................25
3. 偵測靈敏度測試..............................................................................................26
4. 偵測專一性測試..............................................................................................27
5. 偵測感染細胞株測試......................................................................................28
6. 模擬感染血液偵測測試..................................................................................29
八. 一般PCR聚合酶鏈鎖反應................................................................................30
九. DNA 電泳分析...................................................................................................30
十. DNA顯色劑呈色反應........................................................................................31
十一. 試劑......................................................................................................................32
結果......................................................................................................................................33
一. X型扣鎖探針及滾式環形擴增反應..................................................................33
1. 第一型愛滋病B亞型病毒各基因保守序列區域之分析.............................33
2. 扣鎖探針之檢測流程......................................................................................33
3. 扣鎖探針適用量之探討..................................................................................34
4. 探討不同黏合酶對於扣鎖探針檢測之適用性………………….................34
二. Y型恆溫套環式核酸擴增反應..........................................................................35
1. 第一型愛滋病B亞型病毒各基因保守序列區域之分析.............................35
2. 探討gag-specific LAMP assay與vpr-specific LAMP assay
最佳反應溫度..................................................................................................36
3. 探討gag-specific LAMP assay與vpr-specific LAMP assay
反應所需時間..................................................................................................37
4. 探討gag-specific LAMP assay與vpr-specific LAMP assay
偵測之靈敏度..................................................................................................37
5. 探討gag-specific LAMP assay與vpr-specific LAMP assay
偵測之專一性..................................................................................................39
6. 評估gag-specific LAMP assay檢測結果判讀之簡便性..............................39
7. 探討gag-specific LAMP assay與vpr-specific LAMP assay
於感染細胞模式下之偵測能力......................................................................39
8. 探討gag-specific LAMP assay於模擬感染血液模式下之偵測能力.........40
討論.....................................................................................................................................42
參考文獻.............................................................................................................................51
圖.........................................................................................................................................66
表.........................................................................................................................................83
附錄.....................................................................................................................................86
自述.....................................................................................................................................92
參考文獻 (2007) UNAIDS, WHO.

(2011) UNAIDS World AIDS Day Report

Afonso JM, Bello G, Guimaraes ML, Sojka M, Morgado MG (2012) HIV-1 Genetic Diversity and Transmitted Drug Resistance Mutations among Patients from the North, Central and South Regions of Angola. PloS one 7: e42996

Aledort JE, Ronald A, Le Blancq SM, Ridzon R, Landay A, Rafael ME, Shea MV, Safrit J, Peeling RW, Hellmann N, Mwaba P, Holmes K, Wilfert C (2006) Reducing the burden of HIV/AIDS in infants: the contribution of improved diagnostics. Nature 444 Suppl 1: 19-28

Anastassopoulou CG, Touloumi G, Katsoulidou A, Hatzitheodorou H, Pappa M, Paraskevis D, Lazanas M, Gargalianos P, Hatzakis A (2001) Comparative evaluation of the QUANTIPLEX HIV-1 RNA 2.0 and 3.0 (bDNA) assays and the AMPLICOR HIV-1 MONITOR v1.5 test for the quantitation of human immunodeficiency virus type 1 RNA in plasma. Journal of virological methods 91: 67-74

Antson DO, Mendel-Hartvig M, Landegren U, Nilsson M (2003) PCR-generated padlock probes distinguish homologous chromosomes through quantitative fluorescence analysis. European journal of human genetics : EJHG 11: 357-363

Armitage BA (2003) The impact of nucleic acid secondary structure on PNA hybridization. Drug discovery today 8: 222-228

Bagnarelli P, Menzo S, Manzin A, Giacca M, Varaldo PE, Clementi M (1991) Detection of human immunodeficiency virus type 1 genomic RNA in plasma samples by reverse-transcription polymerase chain reaction. Journal of medical virology 34: 89-95

Balamane M, Winters MA, Dalai SC, Freeman AH, Traves MW, Israelski DM, Katzenstein DA, Klausner JD (2010) Detection of HIV-1 in Saliva: Implications for Case-Identification, Clinical Monitoring and Surveillance for Drug Resistance. The open virology journal 4: 88-93

Baner J, Isaksson A, Waldenstrom E, Jarvius J, Landegren U, Nilsson M (2003) Parallel gene analysis with allele-specific padlock probes and tag microarrays. Nucleic acids research 31: e103

Baner J, Marits P, Nilsson M, Winqvist O, Landegren U (2005) Analysis of T-cell receptor V beta gene repertoires after immune stimulation and in malignancy by use of padlock probes and microarrays. Clinical chemistry 51: 768-775

Baner J, Nilsson M, Isaksson A, Mendel-Hartvig M, Antson DO, Landegren U (2001) More keys to padlock probes: mechanisms for high-throughput nucleic acid analysis. Current opinion in biotechnology 12: 11-15

Baner J, Nilsson M, Mendel-Hartvig M, Landegren U (1998) Signal amplification of padlock probes by rolling circle replication. Nucleic acids research 26: 5073-5078

Baner J. GP, et al. (2007) Microarray-based molecular detection of foot-and-mouth disease, vesicular stomatitis and swine vesicular disease viruses, using padlock probes. Virol Methods 143(2): 200-6

Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220: 868-871

Beck IA, Mahalanabis M, Pepper G, Wright A, Hamilton S, Langston E, Frenkel LM (2002) Rapid and sensitive oligonucleotide ligation assay for detection of mutations in human immunodeficiency virus type 1 associated with high-level resistance to protease inhibitors. Journal of clinical microbiology 40: 1413-1419

Berger A, Scherzed L, Sturmer M, Preiser W, Doerr HW, Rabenau HF (2002) Evaluation of the Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test: comparison with the Cobas Amplicor HIV-1 Monitor test (manual specimen preparation). Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 25 Suppl 3: S103-107

Brussel A, Mathez D, Broche-Pierre S, Lancar R, Calvez T, Sonigo P, Leibowitch J (2003) Longitudinal monitoring of 2-long terminal repeat circles in peripheral blood mononuclear cells from patients with chronic HIV-1 infection. AIDS 17: 645-652

Bullard DR, Bowater RP (2006) Direct comparison of nick-joining activity of the nucleic acid ligases from bacteriophage T4. The Biochemical journal 398: 135-144

Bushnell S, Budde J, Catino T, Cole J, Derti A, Kelso R, Collins ML, Molino G, Sheridan P, Monahan J, Urdea M (1999) ProbeDesigner: for the design of probesets for branched DNA (bDNA) signal amplification assays. Bioinformatics 15: 348-355

Chen YJ HY, Chuang SY, Kao DY, Lan YC, Yang JY, Chen YM (2010) Molecular epidemiology of HIV-1 subtype B, CRF01_AE, and CRF07_BC infection among injection drug users in Taiwan. J Acquir Immune Defic Syndr 1;53(4):425-39

Chen YM, Lee CM, Lin RY, Chang HJ (1998) Molecular epidemiology and trends of HIV-1 subtypes in Taiwan. Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association 19: 393-402

Chersich MF, Luchters SM, Othigo MJ, Yard E, Mandaliya K, Temmerman M (2008) HIV testing and counselling for women attending child health clinics: an opportunity for entry to prevent mother-to-child transmission and HIV treatment. International journal of STD & AIDS 19: 42-46

Christian AT, Pattee MS, Attix CM, Reed BE, Sorensen KJ, Tucker JD (2001) Detection of DNA point mutations and mRNA expression levels by rolling circle amplification in individual cells. Proceedings of the National Academy of Sciences of the United States of America 98: 14238-14243

Collins ML, Irvine B, Tyner D, Fine E, Zayati C, Chang C, Horn T, Ahle D, Detmer J, Shen LP, Kolberg J, Bushnell S, Urdea MS, Ho DD (1997) A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml. Nucleic acids research 25: 2979-2984

Dahl F, Baner J, Gullberg M, Mendel-Hartvig M, Landegren U, Nilsson M (2004) Circle-to-circle amplification for precise and sensitive DNA analysis. Proceedings of the National Academy of Sciences of the United States of America 101: 4548-4553

David S, Abbas-Chorfa F, Vanhems P, Vallin B, Iwaz J, Ecochard R (2008) Promotion of WHO feeding recommendations: a model evaluating the effects on HIV-free survival in African children. Journal of human lactation : official journal of International Lactation Consultant Association 24: 140-149

De Cock KM, Fowler MG, Mercier E, de Vincenzi I, Saba J, Hoff E, Alnwick DJ, Rogers M, Shaffer N (2000) Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA : the journal of the American Medical Association 283: 1175-1182

Dewar RL, Highbarger HC, Sarmiento MD, Todd JA, Vasudevachari MB, Davey RT, Jr., Kovacs JA, Salzman NP, Lane HC, Urdea MS (1994) Application of branched DNA signal amplification to monitor human immunodeficiency virus type 1 burden in human plasma. The Journal of infectious diseases 170: 1172-1179

Dickover RE, Garratty EM, Herman SA, Sim MS, Plaeger S, Boyer PJ, Keller M, Deveikis A, Stiehm ER, Bryson YJ (1996) Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load. JAMA : the journal of the American Medical Association 275: 599-605

Dismuke DJ, Aiken C (2006) Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. Journal of virology 80: 3712-3720

Dougherty JP, Temin HM (1988) Determination of the rate of base-pair substitution and insertion mutations in retrovirus replication. Journal of virology 62: 2817-2822

Elbeik T, Alvord WG, Trichavaroj R, de Souza M, Dewar R, Brown A, Chernoff D, Michael NL, Nassos P, Hadley K, Ng VL (2002a) Comparative analysis of HIV-1 viral load assays on subtype quantification: Bayer Versant HIV-1 RNA 3.0 versus Roche Amplicor HIV-1 Monitor version 1.5. J Acquir Immune Defic Syndr 29: 330-339

Elbeik T, Loftus RA, Beringer S (2002b) Health care industries' perspective of viral load assays: the VERSANT HIV-1 RNA 3.0 assay. Expert review of molecular diagnostics 2: 275-285

Enomoto Y, Yoshikawa T, Ihira M, Akimoto S, Miyake F, Usui C, Suga S, Suzuki K, Kawana T, Nishiyama Y, Asano Y (2005) Rapid diagnosis of herpes simplex virus infection by a loop-mediated isothermal amplification method. Journal of clinical microbiology 43: 951-955

FDA Donor screening assays for infectious agents and hiv diagnostic assays. http://www.fda.gov/cber/products/testkits.htm.

Friedman-Kien AE (1981) Disseminated Kaposi's sarcoma syndrome in young homosexual men. Journal of the American Academy of Dermatology 5: 468-471

Fukuta S, Iida T, Mizukami Y, Ishida A, Ueda J, Kanbe M, Ishimoto Y (2003a) Detection of Japanese yam mosaic virus by RT-LAMP. Archives of virology 148: 1713-1720

Fukuta S, Kato S, Yoshida K, Mizukami Y, Ishida A, Ueda J, Kanbe M, Ishimoto Y (2003b) Detection of tomato yellow leaf curl virus by loop-mediated isothermal amplification reaction. Journal of virological methods 112: 35-40

Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M, Richardson E, Kalyanaraman VS, Mann D, Sidhu GD, Stahl RE, Zolla-Pazner S, Leibowitch J, Popovic M (1983) Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 220: 865-867

Gandelman O, Jackson R, Kiddle G, Tisi L (2011) Loop-mediated amplification accelerated by stem primers. International journal of molecular sciences 12: 9108-9124

Gerald L. Mandell JEBaRD (2010) Principles and Practices of Infectious Diseases.

Gilbert PB, McKeague IW, Eisen G, Mullins C, Gueye NA, Mboup S, Kanki PJ (2003) Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal. Statistics in medicine 22: 573-593

Gill P, Ghaemi A (2008) Nucleic acid isothermal amplification technologies: a review. Nucleosides, nucleotides & nucleic acids 27: 224-243

Gingeras TR, Whitfield KM, Kwoh DY (1990) Unique features of the self-sustained sequence replication (3SR) reaction in the in vitro amplification of nucleic acids. Annales de biologie clinique 48: 498-501

Gleaves CA, Welle J, Campbell M, Elbeik T, Ng V, Taylor PE, Kuramoto K, Aceituno S, Lewalski E, Joppa B, Sawyer L, Schaper C, McNairn D, Quinn T (2002) Multicenter evaluation of the Bayer VERSANT HIV-1 RNA 3.0 assay: analytical and clinical performance. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 25: 205-216

Gottlieb MS (2006) Pneumocystis pneumonia--Los Angeles. 1981. American journal of public health 96: 980-981; discussion 982-983

Gyarmati P. CT, et al. (2008) Simultaneous genotyping of all hemagglutinin and neuraminidase subtypes of avian influenza viruses by use of padlock probes. Journal of clinical microbiology 46(5): 1747-51

Hardenbol P, Baner J, Jain M, Nilsson M, Namsaraev EA, Karlin-Neumann GA, Fakhrai-Rad H, Ronaghi M, Willis TD, Landegren U, Davis RW (2003) Multiplexed genotyping with sequence-tagged molecular inversion probes. Nature biotechnology 21: 673-678

Hardenbol P, Yu F, Belmont J, Mackenzie J, Bruckner C, Brundage T, Boudreau A, Chow S, Eberle J, Erbilgin A, Falkowski M, Fitzgerald R, Ghose S, Iartchouk O, Jain M, Karlin-Neumann G, Lu X, Miao X, Moore B, Moorhead M, Namsaraev E, Pasternak S, Prakash E, Tran K, Wang Z, Jones HB, Davis RW, Willis TD, Gibbs RA (2005) Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay. Genome research 15: 269-275

Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Genome research 6: 986-994

Hendricks DA, B. J. Stowe, B. S. Hoo, J. Kolberg, B. D. Irvine, P. D. Neuwald, M. S. Urdea, and R. P. Perrillo. (1995) Quantitation of HBV DNA in human serum using a branched DNA (bDNA) signal amplification assay. Am J Clin Pathol 104:537-546.

Hoffmann C. RJK, et al. Hiv medicine 2007 (Flying Publisher, 2007).

Holguin A, Lopez M, Molinero M, Soriano V (2008) Performance of three commercial viral load assays, Versant human immunodeficiency virus type 1 (HIV-1) RNA bDNA v3.0, Cobas AmpliPrep/Cobas TaqMan HIV-1, and NucliSens HIV-1 EasyQ v1.2, testing HIV-1 non-B subtypes and recombinant variants. Journal of clinical microbiology 46: 2918-2923

Hu WS, Temin HM (1990) Retroviral recombination and reverse transcription. Science 250: 1227-1233

Hymes KB, Cheung T, Greene JB, Prose NS, Marcus A, Ballard H, William DC, Laubenstein LJ (1981) Kaposi's sarcoma in homosexual men-a report of eight cases. Lancet 2: 598-600

Ihira M, Akimoto S, Miyake F, Fujita A, Sugata K, Suga S, Ohashi M, Nishimura N, Ozaki T, Asano Y, Yoshikawa T (2007) Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 39: 22-26

Ihira M, Yoshikawa T, Enomoto Y, Akimoto S, Ohashi M, Suga S, Nishimura N, Ozaki T, Nishiyama Y, Notomi T, Ohta Y, Asano Y (2004) Rapid diagnosis of human herpesvirus 6 infection by a novel DNA amplification method, loop-mediated isothermal amplification. Journal of clinical microbiology 42: 140-145

Imai M, Ninomiya A, Minekawa H, Notomi T, Ishizaki T, Van Tu P, Tien NT, Tashiro M, Odagiri T (2007) Rapid diagnosis of H5N1 avian influenza virus infection by newly developed influenza H5 hemagglutinin gene-specific loop-mediated isothermal amplification method. Journal of virological methods 141: 173-180

Ito M, Watanabe M, Nakagawa N, Ihara T, Okuno Y (2006) Rapid detection and typing of influenza A and B by loop-mediated isothermal amplification: comparison with immunochromatography and virus isolation. Journal of virological methods 135: 272-275

Iwamoto T, Sonobe T, Hayashi K (2003) Loop-mediated isothermal amplification for direct detection of Mycobacterium tuberculosis complex, M. avium, and M. intracellulare in sputum samples. Journal of clinical microbiology 41: 2616-2622

Jayawardena S, Cheung CY, Barr I, Chan KH, Chen H, Guan Y, Peiris JS, Poon LL (2007) Loop-mediated isothermal amplification for influenza A (H5N1) virus. Emerging infectious diseases 13: 899-901

Jonstrup SP, Koch J, Kjems J (2006) A microRNA detection system based on padlock probes and rolling circle amplification. RNA 12: 1747-1752

Jung-Hao Wang LC, Chih-Hung Wang, Wei-Shuo Ling, Shainn-Wei Wang, Gwo-Bin Lee (2012) An integrated chip capable of performing sample pretreatment and nucleic acid amplification for HIV-1 detection. Biosensors and Bioelectronics

Kalin I, Shephard S, Candrian U (1992) Evaluation of the ligase chain reaction (LCR) for the detection of point mutations. Mutation research 283: 119-123

Kaocharoen S, Wang B, Tsui KM, Trilles L, Kong F, Meyer W (2008) Hyperbranched rolling circle amplification as a rapid and sensitive method for species identification within the Cryptococcus species complex. Electrophoresis 29: 3183-3191

Kern D, Collins M, Fultz T, Detmer J, Hamren S, Peterkin JJ, Sheridan P, Urdea M, White R, Yeghiazarian T, Todd J (1996) An enhanced-sensitivity branched-DNA assay for quantification of human immunodeficiency virus type 1 RNA in plasma. Journal of clinical microbiology 34: 3196-3202

Kong F, Tong Z, Chen X, Sorrell T, Wang B, Wu Q, Ellis D, Chen S (2008) Rapid identification and differentiation of Trichophyton species, based on sequence polymorphisms of the ribosomal internal transcribed spacer regions, by rolling-circle amplification. Journal of clinical microbiology 46: 1192-1199

Kono T, Savan R, Sakai M, Itami T (2004) Detection of white spot syndrome virus in shrimp by loop-mediated isothermal amplification. Journal of virological methods 115: 59-65

Kuboki N, Inoue N, Sakurai T, Di Cello F, Grab DJ, Suzuki H, Sugimoto C, Igarashi I (2003) Loop-mediated isothermal amplification for detection of African trypanosomes. Journal of clinical microbiology 41: 5517-5524

Kuhara T, Yoshikawa T, Ihira M, Watanabe D, Tamada Y, Katano H, Asano Y, Matsumoto Y (2007) Rapid detection of human herpesvirus 8 DNA using loop-mediated isothermal amplification. Journal of virological methods 144: 79-85

Kuhn H, Frank-Kamenetskii MD (2005) Template-independent ligation of single-stranded DNA by T4 DNA ligase. The FEBS journal 272: 5991-6000

Kushon SA, Jordan JP, Seifert JL, Nielsen H, Nielsen PE, Armitage BA (2001) Effect of secondary structure on the thermodynamics and kinetics of PNA hybridization to DNA hairpins. Journal of the American Chemical Society 123: 10805-10813

Lal RB, Chakrabarti S, Yang C (2005) Impact of genetic diversity of HIV-1 on diagnosis, antiretroviral therapy & vaccine development. The Indian journal of medical research 121: 287-314

Landegren U, Kaiser R, Sanders J, Hood L (1988) A ligase-mediated gene detection technique. Science 241: 1077-1080

Larsson C, Koch J, Nygren A, Janssen G, Raap AK, Landegren U, Nilsson M (2004) In situ genotyping individual DNA molecules by target-primed rolling-circle amplification of padlock probes. Nature methods 1: 227-232

Li WH TM, Sharp PM (1988) Rates and dates of divergence between AIDS virus nucleotide sequences. Mol Biol Evol 5(4):313-30.

Lihana RW, Ssemwanga D, Abimiku A, Ndembi N (2012) Update on HIV-1 diversity in Africa: a decade in review. AIDS reviews 14: 83-100

Lizardi PM, Huang X, Zhu Z, Bray-Ward P, Thomas DC, Ward DC (1998) Mutation detection and single-molecule counting using isothermal rolling-circle amplification. Nature genetics 19: 225-232

Mahmoudian L, Kaji N, Tokeshi M, Nilsson M, Baba Y (2008) Rolling circle amplification and circle-to-circle amplification of a specific gene integrated with electrophoretic analysis on a single chip. Analytical chemistry 80: 2483-2490

Marciniak J, Kummel A, Esener S, Heller M, Messmer B (2008) Coupled rolling circle amplification loop-mediated amplification for rapid detection of short DNA sequences. BioTechniques 45: 275-280

Maruyama F, Kenzaka T, Yamaguchi N, Tani K, Nasu M (2003) Detection of bacteria carrying the stx2 gene by in situ loop-mediated isothermal amplification. Applied and environmental microbiology 69: 5023-5028

McCarthy EL, Egeler TJ, Bickerstaff LE, Pereira da Cunha M, Millard PJ (2006) Detection and identification of IHN and ISA viruses by isothermal DNA amplification in microcapillary tubes. Analytical and bioanalytical chemistry 386: 1975-1984

McDermott JL, Martini I, Ferrari D, Bertolotti F, Giacomazzi C, Murdaca G, Puppo F, Indiveri F, Varnier OE (2005) Decay of human immunodeficiency virus type 1 unintegrated DNA containing two long terminal repeats in infected individuals after 3 to 8 years of sustained control of viremia. Journal of clinical microbiology 43: 5272-5274

Millard PJ, Bickerstaff LE, LaPatra SE, Kim CH (2006) Detection of infectious haematopoietic necrosis virus and infectious salmon anaemia virus by molecular padlock amplification. Journal of fish diseases 29: 201-213

Mofenson LM, McIntyre JA (2000) Advances and research directions in the prevention of mother-to-child HIV-1 transmission. Lancet 355: 2237-2244

Mora JR, Getts RC (2007) High-sensitivity detection methods for low-abundance RNA species: applications for functional genomics research. Expert review of molecular diagnostics 7: 775-785

Mori N, Motegi Y, Shimamura Y, Ezaki T, Natsumeda T, Yonekawa T, Ota Y, Notomi T, Nakayama T (2006) Development of a new method for diagnosis of rubella virus infection by reverse transcription-loop-mediated isothermal amplification. Journal of clinical microbiology 44: 3268-3273

Mori Y, Nagamine K, Tomita N, Notomi T (2001) Detection of loop-mediated isothermal amplification reaction by turbidity derived from magnesium pyrophosphate formation. Biochemical and biophysical research communications 289: 150-154

Mukherjee JS, Farmer PE, Niyizonkiza D, McCorkle L, Vanderwarker C, Teixeira P, Kim JY (2003) Tackling HIV in resource poor countries. BMJ 327: 1104-1106

Mullis KB, Faloona FA (1987) Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods in enzymology 155: 335-350

Nagamine K, Hase T, Notomi T (2002) Accelerated reaction by loop-mediated isothermal amplification using loop primers. Molecular and cellular probes 16: 223-229

Neil S, Martin F, Ikeda Y, Collins M (2001) Postentry restriction to human immunodeficiency virus-based vector transduction in human monocytes. Journal of virology 75: 5448-5456

Nilsson M, Antson DO, Barbany G, Landegren U (2001) RNA-templated DNA ligation for transcript analysis. Nucleic acids research 29: 578-581

Nilsson M, Barbany G, Antson DO, Gertow K, Landegren U (2000) Enhanced detection and distinction of RNA by enzymatic probe ligation. Nature biotechnology 18: 791-793

Nilsson M, Krejci K, Koch J, Kwiatkowski M, Gustavsson P, Landegren U (1997) Padlock probes reveal single-nucleotide differences, parent of origin and in situ distribution of centromeric sequences in human chromosomes 13 and 21. Nature genetics 16: 252-255

Nilsson M, Malmgren H, Samiotaki M, Kwiatkowski M, Chowdhary BP, Landegren U (1994) Padlock probes: circularizing oligonucleotides for localized DNA detection. Science 265: 2085-2088

Nilsson M. BJ, et al. (2002) Making ends meet in genetic analysis using padlock probes. Hum Mutat 19(4): 410-5.

Nilsson M. DF, et al. (2006) Analyzing genes using closing and replicating circles. Trends Biotechnol 24(2): 83-8

Notomi T, Okayama H, Masubuchi H, Yonekawa T, Watanabe K, Amino N, Hase T (2000) Loop-mediated isothermal amplification of DNA. Nucleic acids research 28: E63

Okafuji T, Yoshida N, Fujino M, Motegi Y, Ihara T, Ota Y, Notomi T, Nakayama T (2005) Rapid diagnostic method for detection of mumps virus genome by loop-mediated isothermal amplification. Journal of clinical microbiology 43: 1625-1631

Parida M, Horioke K, Ishida H, Dash PK, Saxena P, Jana AM, Islam MA, Inoue S, Hosaka N, Morita K (2005) Rapid detection and differentiation of dengue virus serotypes by a real-time reverse transcription-loop-mediated isothermal amplification assay. Journal of clinical microbiology 43: 2895-2903

Pas S, Rossen JW, Schoener D, Thamke D, Pettersson A, Babiel R, Schutten M (2010) Performance evaluation of the new Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 for quantification of human immunodeficiency virus type 1 RNA. Journal of clinical microbiology 48: 1195-1200

Pathak VK, Temin HM (1990a) Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: deletions and deletions with insertions. Proceedings of the National Academy of Sciences of the United States of America 87: 6024-6028

Pathak VK, Temin HM (1990b) Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations. Proceedings of the National Academy of Sciences of the United States of America 87: 6019-6023

Poon LL, Leung CS, Tashiro M, Chan KH, Wong BW, Yuen KY, Guan Y, Peiris JS (2004) Rapid detection of the severe acute respiratory syndrome (SARS) coronavirus by a loop-mediated isothermal amplification assay. Clinical chemistry 50: 1050-1052

Prins TW, van Dijk JP, Beenen HG, Van Hoef AA, Voorhuijzen MM, Schoen CD, Aarts HJ, Kok EJ (2008) Optimised padlock probe ligation and microarray detection of multiple (non-authorised) GMOs in a single reaction. BMC genomics 9: 584

Reeves JD, Doms RW (2002) Human immunodeficiency virus type 2. The Journal of general virology 83: 1253-1265

Regoes RR, Wodarz D, Nowak MA (1998) Virus dynamics: the effect of target cell limitation and immune responses on virus evolution. Journal of theoretical biology 191: 451-462

Rodriguez-Sanchez B. S-VJM, et al. (2008) Improved diagnosis for nine viral diseases considered as notifiable by the world organization for animal health. Transbound Emerg Dis 55(5-6): 215-25

Ross RS, Viazov S, Sarr S, Hoffmann S, Kramer A, Roggendorf M (2002) Quantitation of hepatitis C virus RNA by third generation branched DNA-based signal amplification assay. Journal of virological methods 101: 159-168

Ruelle J, Jnaoui K, Lefevre I, Lamarti N, Goubau P (2009) Comparative evaluation of the VERSANT HIV-1 RNA 1.0 kinetic PCR molecular system (kPCR) for the quantification of HIV-1 plasma viral load. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 44: 297-301

Savan R, Igarashi A, Matsuoka S, Sakai M (2004) Sensitive and rapid detection of edwardsiellosis in fish by a loop-mediated isothermal amplification method. Applied and environmental microbiology 70: 621-624

Shafer RW, Hsu P, Patick AK, Craig C, Brendel V (1999) Identification of biased amino acid substitution patterns in human immunodeficiency virus type 1 isolates from patients treated with protease inhibitors. Journal of virology 73: 6197-6202

Stougaard M, Lohmann JS, Zajac M, Hamilton-Dutoit S, Koch J (2007) In situ detection of non-polyadenylated RNA molecules using Turtle Probes and target primed rolling circle PRINS. BMC biotechnology 7: 69

Swanson P, Huang S, Holzmayer V, Bodelle P, Yamaguchi J, Brennan C, Badaro R, Brites C, Abravaya K, Devare SG, Hackett J, Jr. (2006) Performance of the automated Abbott RealTime HIV-1 assay on a genetically diverse panel of specimens from Brazil. Journal of virological methods 134: 237-243

Szemes M, Bonants P, de Weerdt M, Baner J, Landegren U, Schoen CD (2005) Diagnostic application of padlock probes--multiplex detection of plant pathogens using universal microarrays. Nucleic acids research 33: e70

Tanchou V, Decimo D, Pechoux C, Lener D, Rogemond V, Berthoux L, Ottmann M, Darlix JL (1998) Role of the N-terminal zinc finger of human immunodeficiency virus type 1 nucleocapsid protein in virus structure and replication. Journal of virology 72: 4442-4447

Temin HM (1993) Retrovirus variation and reverse transcription: abnormal strand transfers result in retrovirus genetic variation. Proceedings of the National Academy of Sciences of the United States of America 90: 6900-6903

Teo I. A. MJ, et al. (2002) Reliable and reproducible lightcycler qpcr for hiv-1 DNA 2-ltr circles. Journal of immunological methods 270(1): 109-18.

Todd J, C. Pachl, R. White, T. Yeghiazarian, P. Johnson, B. Taylor, M. Holodniy, D. Kern, S. Hamren, D. Chernoff, et al. (1995) Performance characteristics for the quantitation of plasma HIV-1 RNA using branched DNA signal amplification technology. J Acquir Immune Defic Syndr Hum Retrovirol 10(Suppl. 2):S35-S44.

Toriniwa H, Komiya T (2006) Rapid detection and quantification of Japanese encephalitis virus by real-time reverse transcription loop-mediated isothermal amplification. Microbiology and immunology 50: 379-387

Urdea M, Penny LA, Olmsted SS, Giovanni MY, Kaspar P, Shepherd A, Wilson P, Dahl CA, Buchsbaum S, Moeller G, Hay Burgess DC (2006) Requirements for high impact diagnostics in the developing world. Nature 444 Suppl 1: 73-79

van Deursen P, Oosterlaken T, Andre P, Verhoeven A, Bertens L, Trabaud MA, Ligeon V, de Jong J (2010) Measuring human immunodeficiency virus type 1 RNA loads in dried blood spot specimens using NucliSENS EasyQ HIV-1 v2.0. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 47: 120-125

van Eijk MJ, Broekhof JL, van der Poel HJ, Hogers RC, Schneiders H, Kamerbeek J, Verstege E, van Aart JW, Geerlings H, Buntjer JB, van Oeveren AJ, Vos P (2004) SNPWave: a flexible multiplexed SNP genotyping technology. Nucleic acids research 32: e47

van Gemen B, Kievits T, Schukkink R, van Strijp D, Malek LT, Sooknanan R, Huisman HG, Lens P (1993) Quantification of HIV-1 RNA in plasma using NASBA during HIV-1 primary infection. Journal of virological methods 43: 177-187

Wang B, Potter SJ, Lin Y, Cunningham AL, Dwyer DE, Su Y, Ma X, Hou Y, Saksena NK (2005) Rapid and sensitive detection of severe acute respiratory syndrome coronavirus by rolling circle amplification. Journal of clinical microbiology 43: 2339-2344

Zhang DY, Zhang W, Li X, Konomi Y (2001) Detection of rare DNA targets by isothermal ramification amplification. Gene 274: 209-216

Zhong XB, Lizardi PM, Huang XH, Bray-Ward PL, Ward DC (2001) Visualization of oligonucleotide probes and point mutations in interphase nuclei and DNA fibers using rolling circle DNA amplification. Proceedings of the National Academy of Sciences of the United States of America 98: 3940-3945

Zhou X, Kong F, Sorrell TC, Wang H, Duan Y, Chen SC (2008) Practical method for detection and identification of Candida, Aspergillus, and Scedosporium spp. by use of rolling-circle amplification. Journal of clinical microbiology 46: 2423-2427

Zhou Y. CM, et al. (2001) In situ detection of messenger rna using digoxigenin-labeled oligonucleotides and rolling circle amplification. Exp Mol Pathol 70(3): 281-8

Zlateva KT, Crusio KM, Leontovich AM, Lauber C, Claas E, Kravchenko AA, Spaan WJ, Gorbalenya AE (2011) Design and validation of consensus-degenerate hybrid oligonucleotide primers for broad and sensitive detection of corona- and toroviruses. Journal of virological methods 177: 174-183
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