SIGNAL AMPLIFICATION TECHNIQUES AND APPLICATIONS IN DIAGNOSTIC VIROLOGY

Abstract

Signal amplification methods are the most preferred non-PCR molecular tools in diagnostic virology. The aim of signal amplification tests is to amplify and measure the signals obtained from the target DNA or RNA in clinical samples, instead of directly copying these molecules. With these characteristics, signal amplification methods do not pose any risk of contamination of the test samples, laboratory devices or working environment with amplified products. Approved signal amplification tests have been commercially available for detection and quantitation of HIV-1, HCV and HPV nucleic acids, as well as genotyping analysis of HPV. Signal amplification tests were first used in the early 1990s and have different working principles and special designs. These tests are now combined with new diagnostic techniques such as real-time PCR, the rolling circle method, luminex xMAP, DNA biosensor technology and sequence analysis, in the detection and genotyping of viral agents, multiplex analysis and the discovery of new and unknown viruses. In addition, approved signal amplification tests are used as the standard control methods for newly developed test designs. In this review, the working principles of signal amplification-based tests and their use in diagnostic virology are discussed in detail and examples of their use in other platforms are presented. 

Keywords

• Branched DNA
• Hybrid capture
• Invader

SİNYAL AMPLİFİKASYON TEKNİKLERİ VE TANISAL VİROLOJİDEKİ UYGULAMALARI

Abstract

Tanısal virolojide PCR dışı moleküler araçlar arasında ilk sırada sinyal amplifikasyon yöntemleri yer almaktadır. Sinyal amplifikasyon testlerinde klinik örneklerdeki hedef DNA veya RNA’nın doğrudan kopyalanması yerine, bu moleküllerden elde edilen sinyallerin yükseltilmesi ve ölçülmesi amaçlanır. Bu özellikleri ile sinyal amplifikasyon yöntemleri incelenecek örnekler, kullanılan gereçler veya çalışma ortamının amplifiye ürünlerle kontamine olması bakımından risk taşımazlar. HIV-1, HCV ve HPV nükleik asitlerinin saptanması ve kantitasyonu ve HPV genotip analizi için onaylı sinyal amplifikasyon testleri ticari olarak kullanıma sunulmuştur. İlk olarak 1990’lı yılların başlarında kullanılmaya başlanan ve farklı çalışma prensipleri ve özel tasarımlara sahip olan sinyal amplifikasyon testleri günümüzde real-time PCR, rolling circle yöntemi, luminex xMAP, DNA biyosensör teknolojisi ve dizi analizi gibi yeni tanısal tekniklerle kombine edilerek viral etkenlerin saptanması, genotiplendirilmesi, multipleks analizleri ve bilinmeyen yeni virusların keşfedilmesinde kullanılmaktadır. Onaylı sinyal amplifikasyon testleri yeni geliştirilen test tasarımları için standart kontrol yöntemleri olarak da kullanılmaktadır. Bu derlemede sinyal amplifikasyon temelli testlerin çalışma prensipleri ve tanısal virolojideki kullanımları detaylı olarak ele alınmış ve diğer platformlardaki kullanımlarına dair örnekler sunulmuştur.

Keywords

• Dallı DNA
• Hibrid yakalama
• İnvader

References

1. 1. Handricks DA, Comanor L. Signal Amplification-Based Techniques. In: Lorincz A, editor. Nucleic Acid Testing for Human Disease. New York: CRC/Taylor & Francis; 2006:1964.
2. 2. Gullett JC, Nolte FS. Quantitative Nucleic Acid Amplification Methods for Viral Infections. Clin Chem 2015;61(1):72-8.
3. 3. Şahiner F, Gümral R, Yıldızoğlu Ü, Babayiğit MA, Durmaz A, Yiğit N, et al. Coexistence of Epstein-Barr virus and Parvovirus B19 in tonsillar tissue samples: Quantitative measurement by real-time PCR. Int J Pediatr Otorhinolaryngol 2014;78(8):1288-93. [CrossRef]
4. 4. Nolte F, Wittwer C. Nucleic Acid Amplification Methods Overview. In: Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, et al, editors. Molecular Microbiology. Washington, USA: ASM Press; 2016:3-18.
5. 5. Niesters HGM, van Leeuwen WB. Quantitative Isothermal Molecular Amplification Techniques (Chapter 7). In: van Pelt-Verkuil E, van Leeuwen WB, Witt R, editors. Molecular Diagnostics. Singapore: Springer; 2019:321-37. [CrossRef]
6. 6. Şahiner F, Şener K, Gümral R, Yapar M, Dede M, Yiğit N, et al. Üç farklı real-time PCR testinin karşılaştırmalı sonuçları: MY09/11 primerleri çoklu enfeksiyonları kaçırıyor. Gulhane Med J 2014;56(2):65-70. [CrossRef]
7. 7. Yan L, Zhou J, Zheng Y, Gamson AS, Roembke BT, Nakayama S, et al. Isothermal amplified detection of DNA and RNA. Mol Biosyst 2014;10(5):970-1003. [CrossRef] 8. Wang YF. Signal Amplification Techniques: bDNA, Hybrid Capture. In: Tang YW, Stratton CW, editors. Advanced Techniques in Diagnostic Microbiology. USA: Springer; 2006:228-42. [CrossRef]
8. 9. Jin F, Li H, Xu D. Enzyme-free fluorescence microarray for determination of hepatitis B virus DNA based on silver nanoparticle aggregates-assisted signal amplification. Anal Chim Acta 2019;1077:297-304. [CrossRef]

9. 10. Emmadi R, Boonyaratanakornkit JB, Selvarangan R, Shyamala V, Zimmer BL, Williams L, et al. Molecular methods and platforms for infectious diseases testing a review of FDA-approved and cleared assays. J Mol Diagn 2011;13(6):583-604. [CrossRef]
10. 11. Şahiner F. Genital İnsan Papillomavirus Enfeksiyonlarının Moleküler Tanısında Karşılaşılan Sorunlar ve Yeni Gelişmeler. Mikrobiyol Bul 2014;48(4):689-706. [CrossRef]
11. 12. van der Sluis RM, van Montfort T, Centlivre M, Schopman NC, Cornelissen M, Sanders RW, et al. Quantitation of HIV-1 DNA with a sensitive TaqMan assay that has broad subtype specificity. J Virol Methods 2013;187(1):94-102. [CrossRef]
12. 13. Gokahmetoglu S, Deniz E, Ozbal Y, Atalay AM. Comparison of branched DNA and real-time polymerase chain reaction methods in quantitation of hepatitis B virus DNA. Saudi Med J 2007;28(11):1750-1.
13. 14. Boeckh M, Boivin G. Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev 1998;11(3):533-54. [CrossRef]
14. 15. Collins ML, Irvine B, Tyner D, et al. A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml. Nucleic Acids Res 1997;25(15):2979-84. [CrossRef]
15. 16. Bushnell S, Budde J, Catino T, et al. ProbeDesigner: for the design of probesets for branched DNA (bDNA) signal amplification assays. Bioinformatics 1999;15(5):348-55. [CrossRef]
16. 17. Sarrazin C, Gärtner BC, Sizmann D, Babiel R, Mihm U, Hofmann WP, et al. Comparison of conventional PCR with real-time PCR and branched DNA-based assays for hepatitis C virus RNA quantification and clinical significance for genotypes 1 to 5. J Clin Microbiol 2006;44(3):729-37. [CrossRef]
17. 18. Pellegrin I, Garrigue I, Binquet C, Chene G, Neau D, Bonot P, et al. Evaluation of new quantitative assays for diagnosis and monitoring of cytomegalovirus disease in human immunodeficiency virus-positive patients. J Clin Microbiol 1999;37(10):3124-32.
18. 19. Cha W, Ma Y, Saif YM, Lee CW. Development of microsphere-based multiplex branched DNA assay for detection and differentiation of avian influenza virus strains. J Clin Microbiol 2010;48(7):2575-7. [CrossRef]
19. 20. Davies J, Maqsodi B, Yang W, Ma Y, Luo Y, McMaster G.P25-S Gene Expression Profiling from Formalin-Fixed, ParaffinEmbedded Tissues Using the QuantiGene Branched DNA Assay. J Biomol Tech 2007;18(1):9.
20. 21. Zhang A, Pastor L, Nguyen Q, Luo Y, Yang W, Flagella M, et al. Small interfering RNA and gene expression analysis using a multiplex branched DNA assay without RNA purification. J Biomol Screen; 2005:10:549-56. [CrossRef]
21. 22. Harvey JJ, Lee SP, Chan EK, et al. Characterization and applications of CataCleave probe in real-time detection assays. Anal Biochem 2004;333(2):246-55. [CrossRef]
22. 23. Ihira M, Yamaki A, Kato Y, Higashimoto Y, Kawamura Y, Yoshikawa T. Cycling probe-based real-time PCR for the detection of Human herpesvirus 6A and B. J Med Virol 2016;88(9):1628-35. [CrossRef]
23. 24. Ihira M, Higashimoto Y, Kawamura Y, Sugata K, Ohashi M, Asano Y, et al. Cycling probe technology to quantify and discriminate between wild-type varicella-zoster virus and Oka vaccine strains. J Virol Methods 2013;193(2):308-13. [CrossRef]
24. 25. Uchida Y, Kouyama J, Naiki K, Sugawara K, Ando S, Nakao M, et al. Significance of variants associated with resistance to NS5A inhibitors in Japanese patients with genotype 1b hepatitis C virus infection as evaluated using cyclingprobe real-time PCR combined with direct sequencing. J Gastroenterol 2016;51(3):260-70. [CrossRef]
25. 26. Suzuki Y, Saito R, Zaraket H, Dapat C, Caperig-Dapat I, Suzuki H. Rapid and specific detection of amantadineresistant influenza A viruses with a Ser31Asn mutation by the cycling probe method. J Clin Microbiol 2010;48(1):5763. [CrossRef]
26. 27. Suzuki Y, Saito R, Sato I, Zaraket H, Nishikawa M, Tamura T, et al. Identification of oseltamivir resistance among pandemic and seasonal influenza A (H1N1) viruses by an His275Tyr genotyping assay using the cycling probe method. J Clin Microbiol 2011;49(1):125-30. [CrossRef]
27. 28. Us, D. New, newer, newest human polyomaviruses: how far?. Mikrobiol Bul 2013;47(2):362-81. [CrossRef]
28. 29. HC2 High-Risk HPV DNA Test. Digene Catalog Number 51011296. Digene Corporation Gaithersburg, MD USA, 2002.
29. 30. Molijn A, Kleter B, Quint W, van Doorn LJ. Molecular diagnosis of human papillomavirus (HPV) infections. J Clin Virol 2005;32(Suppl 1):S43-51. [CrossRef]
30. 31. Gravitt PE, Viscidi RP. Measurement of Exposure to Human Papillomaviruses (Chapter 5). In: Rohan TE, Shah KV, editors. Cervical Cancer: From Etiology to Prevention (Cancer Prevention-Cancer Causes). Boston: Kluwer Academic Publishers; 2004:119-41. [CrossRef]
31. 32. Eder PS, Lou J, Huff J, Macioszek J. The next-generation Hybrid Capture High-Risk HPV DNA assay on a fully automated platform. J Clin Virol 2009;45(Suppl 1):S85-92. [CrossRef]
32. 33. Maasoumy B, Vermehren J. Diagnostics in hepatitis C: The end of response-guided therapy? J Hepatol 2016;65(1 Suppl):S67-S81. [CrossRef]
33. 34. Allice T, Cerutti F, Pittaluga F, Varetto S, Gabella S, Marzano A, et al. Comparison of the Cobas Ampliprep/Cobas TaqMan HBV Test versus the Cobas Amplicor HBV monitor for HBV-DNA detection and quantification during antiviral therapy. New Microbiol 2008;31(1):27-35.
34. 35. Tadokoro K, Yamaguchi T, Egashira T, Hara T. Quantitation of viral load by real-time PCR-monitoring Invader reaction. J Virol Methods 2009;155(2):182-6. [CrossRef]
35. 36. Germer JJ, Majewski DW, Yung B, Mitchell PS, Yao JD. Evaluation of the invader assay for genotyping hepatitis C virus. J Clin Microbiol 2006;44(2):318-23. [CrossRef]
36. 37. Wong DK, Yuen MF, Yuan H, Sum SS, Hui CK, Hall J, et al. Quantitation of covalently closed circular hepatitis B virus DNA in chronic hepatitis B patients. Hepatology 2004;40(3):727-37. [CrossRef]
37. 38. Constantine NT, Kabat W, Zhao RY. Update on the laboratory diagnosis and monitoring of HIV infection. Cell Res 2005;15(11-12):870-6. [CrossRef]
38. 39. Stillman MJ, Day SP. Schutzbank TE. A comparative review of laboratory-developed tests utilizing Invader HPV analyte-specific reagents for the detection of high-risk human papillomavirus. J Clin Virol 2009;45(Suppl 1):S73-7. [CrossRef]
39. 40. Poljak M, Kocjan BJ. Commercially available assays for multiplex detection of alpha human papillomaviruses. Expert Rev Anti Infect Ther 2010;8(10):1139-62. [CrossRef] 41. Garrigues HJ, Rubinchikova YE, Rose TM. KSHV cell attachment sites revealed by ultra sensitive tyramide signal amplification (TSA) localize to membrane microdomains that are up-regulated on mitotic cells. Virology 2014;452453:75-85. [CrossRef] 42. Kotronias D, Kapranos N. Herpes simplex virus as a determinant risk factor for coronary artery atherosclerosis and myocardial infarction. In Vivo 2005;19(2):351-7. 43. Strappe PM, Wang TH, McKenzie CA, Lowrie S, Simmonds P, Bell JE. Enhancement of immunohistochemical detection of HIV-1 p24 antigen in brain by tyramide signal amplification. J Virol Methods 1997;67(1):103-12. [CrossRef]
40. 44. Zhan L, Yang T, Li CM, Wu WB, Huang CZ. Sensitive immunosensor for respiratory syncytial virus based on dual signal amplification of gold nanopaticle layer-modified plates and catalyzed reporter deposition. Sens Actuators B Chem 2018;255(2):1291-7. [CrossRef]
41. 45. Treadway CR, Michael GH, Jacqueline KB. Charge transport through a molecular π-stack: double helical DNA. Chemical Physics 2002;281(2-3):409-28. [CrossRef]
42. 46. Gorodetsky AA, Buzzeo MC, Barton JK. DNA-mediated electrochemistry. Bioconjug Chem 2008;19(12):2285-96. [CrossRef]
43. 47. Genereux JC, Barton JK. Mechanisms for DNA charge transport. Chem Rev 2010;110(3):1642-62. [CrossRef]
44. 48. Karash S, Wang R, Kelso L, Lu H, Huang TJ, Li Y. Rapid detection of avian influenza virus H5N1 in chicken tracheal samples using an impedance aptasensor with gold nanoparticles for signal amplification. J Virol Methods 2016;236:147-56. [CrossRef]
45. 49. Abolhasan R, Mehdizadeh A, Rashidi MR, Aghebati-Maleki L, Yousefi M. Application of hairpin DNA-based biosensors with various signal amplification strategies in clinical diagnosis. Biosens Bioelectron 2019;129:164-74. [CrossRef]
46. 50. Lu M, Xu L, Zhang X, Xiao R, Wang Y. Ag(I)-coordinated hairpin DNA for homogenous electronic monitoring of hepatitis C virus accompanying isothermal cycling signal amplification strategy. Biosens Bioelectron 2015;73:195201