臺灣博碩士論文加值系統

第一型人類免疫缺乏病毒 (type 1 human immunodeficiency virus, HIV-1) 自1981年被公布於世至今，已成為當代最為嚴重的傳染疾病之一。即使在高效能抗反轉錄病毒療法已問世並大為普及的現代，HIV-1與 AIDS (acquired immune deficiency syndrome) 依然在不同社會與健康議題層面上有許多尚待解決的問題。據此，本研究欲分別從分子流行病學、鑑識科學與方法學等各面向進行HIV-1 相關議題的探討。在流行病學監測的部分，我們於2013-2015年間從大台北與高雄地區參與匿名篩檢的男男間性行為者中進行個案招募。共計有 4,675 位個案參與，HIV-1總盛行率為 4.3% (201/4675)，並發現盛行率與發生率有逐年下降的趨勢，且與保護性行為因子之變化顯著相關。系統發生樹分析結果顯示不同風險族群於國內及國際間的交流有助長HIV-1傳播的可能。在傳染方向性鑑定的研究部分，其為國內首次將maximum likelihood 與 Bayesian系統發生樹分析結果作為鑑識證據呈現於法庭之案例，共有三個來自不同法庭之法律案件參與。我們亦比較了傳統以分子轉殖方式與高通量焦磷酸測序 (ultra-deep pyrosequencing, UDPS) 技術取得病毒基因序列在分析上的差異。結果顯示分子轉殖取得序列之結果可清楚呈現案件ㄧ與三之方向性，惟案件二因採血時間點延遲，需結合UDPS技術取得序列分析方可進一步輔助來源鑑定。我們的結果亦呈現了UDPS在方向性分析應用上的限制與不足，有待進一步改進。在單一病毒顆粒追蹤系統的研究中，我們意圖發展ㄧ以量子點 (Quantum-dots, QDs) 為基礎之病毒標記模型，並應用於3D多解析度即時單一顆粒追蹤系統中。此模型基於ㄧ帶有8個組胺酸重複標記之pCMVΔR8.91質體，並使其在病毒自組裝過程中與QDs結合，以偵測及紀錄其 3D 移動軌跡，最後與雙光子顯微鏡即時掃描影像所建模的宿主細胞微環境模型疊合，便可呈現病毒與宿主細胞的交互作用。截至當前，我們已取得ㄧ完整的單病毒軌跡，其在自由擴散狀態、細胞貼附期，以及病毒配體與細胞表面受器錨定後之移動過程皆已被成功記錄。

Since it has been revealed and reported to the human society at 1981, HIV-1 has become one of the most serious transmitted diseases of all time worldwide. Even with the emergence of highly active antiretroviral therapy, several issues have been implicated with HIV-1 on different levels. This study investigated HIV-1 in distinct aspects, including molecular epidemiology, forensic science, and virological methodology. In the surveillance part, we recruited men who have sex with men (MSM) subjects in northern and southern Taiwan for anonymous HIV-1 screening during 2013–2015. In total, 4675 subjects were enrolled. The annual prevalence and incidence of HIV-1 showed a downward trend, which was associated with protective factors. Phylogenetic tree analysis showed that the cross-regional and international interactions of the local MSM population may have facilitated the transmission of HIV-1. The second part introduced phylogenetic tree results as forensic evidence in a trial in Taiwan for the first time. Three lawsuit cases were involved. We identified the source of transmission in each lawsuit based on the maximum likelihood and Bayesian phylogenetic tree analyses using the sequences from molecular cloning and ultra-deep pyrosequencing (UDPS). The results of phylogenetic analysis using molecular cloning sequences were clear in lawsuits 1 and 3. Due to the delayed sampling, the transmission direction of lawsuit 2 could not be confirmed unless it was combined with the UDPS sequences results. However, the validity and evidential effects of the UDPS method application were still limited and need further optimization. In the third part, we aimed to develop a quantum dots (QD)-based virion labeling method that is trackable with living cells via a novel 3D multi-resolution real-time single particle tracking system. A QD- pCMVΔR8.91 plasmid that can be labeled was cloned. Currently, a single-virion trajectory containing free diffusion, cell membrane attachment, and docking-like process between the virion and the host cell has been recorded successfully.

Abstract iv
Contents viii
List of Figures xi
List of Tables xii
List of Appendix Figures and Tables xiii
List of Abbreviation xv
I. General Introduction 16
I-1 Molecular Epidemiology of HIV-1 Infection：Global Distribution and The Situation in Taiwan 17
I-2 HIV-1 Genomic Structure and Life Cycle 20
I-3 The Phylogenetic Analysis in HIV-1 Research and Forensic Science 22
I-4 The Development of Real-Time Live-Cell Single Virus Tracking 24
I-5 Study Goals and Aims 27
II. Materials and Methods 30
II-1 Aim 1 - Molecular Epidemiology of HIV-1 Infection among Men who have Sex with Men in Taiwan from 2013 to 2015 31
II-1-1 Subjects enrollment and data collection 31
II-1-2 Determination of HIV-1 genotypes 31
II-1-3 Phylogenetic tree analysis 32
II-1-4 Nucleotide sequence accession numbers 32
II-1-5 LAg-avidity EIA test and incidence rate calculation 32
II-1-6 Statistical analysis 33
II-2 Aim 2 - The Application of Phylogenetic Analysis for Source Identification in Three HIV-1 Transmission Lawsuits in Taiwan 34
II-2-1 Lawsuit cases subjects 34
II-2-2 DNA extraction, polymerase chain reaction (PCR) condition, molecular cloning and sequencing 34
II-2-3 GenBank control and local control references 35
II-2-4 UDPS procedure, sequences analysis and bioinformatics 35
II-2-5 Phylogenetic methods 36
II-2-6 Nucleotide sequence accession numbers 37
II-3 Aim 3 - Development of HIV-1 Virion Real-Time Tracking Model via Multi-Resolution Microscope and Quantum Dot Encapsulation 38
II-3-1 Cell-line and plasmid 38
II-3-2 Multi-resolution two-photon microscope 38
II-3-3 The single QD-encapsulated virion real-time tracking 39
III. Results 41
III-1 Aim 1 - Molecular Epidemiology of HIV-1 Infection among Men who have Sex with Men in Taiwan from 2013 to 2015 42
III-1-1 Annual trend of prevalence and incidence rates 42
III-1-2 Genotyping and phylogenetic tree analysis 44
III-1-3 Univariate and multivariate logistic regression analysis 46
III-1-4 Cochran-Armitage trend test 50
III-1-5 Univariate and multivariate logistic regression analysis of recreational drug user in MSM 52
III-2 Aim 2 - The Application of Phylogenetic Analysis for Source Identification in Three HIV-1 Transmission Lawsuits in Taiwan 61
III-2-1 Clinical data and contact history 61
III-2-2 Phylogenetic tree analysis 61
III-2-3 Phylogenetic tree analysis using the sequences from molecular cloning 63
III-2-4 Phylogenetic tree analysis using sequences from UDPS 65
III-3 Aim 3 - Development of HIV-1 Virion Real-Time Tracking Model via Multi-Resolution Microscope and Quantum Dot Encapsulation 70
III-3-1 The generation of QD-encapsulated virion 70
III-3-2 The real-time tracking of QD-encapsulated virion via multi-resolution microscopy 74
IV. Discussion 79
IV-1 Aim 1 - Molecular Epidemiology of HIV-1 Infection among Men who have Sex with Men in Taiwan from 2013 to 2015 80
IV-2 Aim 2 - The Application of Phylogenetic Analysis for Source Identification in Three HIV-1 Transmission Lawsuits in Taiwan 85
IV-3 Aim 3 - Development of HIV-1 Virion Real-Time Tracking Model via Multi-Resolution Microscope and Quantum Dot Encapsulation 93
V. Conclusion 97
Reference 100
Appendix Figures and Tables 110
Publications 129

1. Aggleton P., and Parker R.: Moving Beyond Biomedicalization in the HIV Response: Implications for Community Involvement and Community Leadership Among Men Who Have Sex with Men and Transgender People. Am J Public Health 2015; 105: pp. 1552-8
2. Albert J., Wahlberg J., Leitner T., Escanilla D., and Uhlen M.: Analysis of a rape case by direct sequencing of the human immunodeficiency virus type 1 pol and gag genes. J Virol 1994; 68: pp. 5918-24
3. Altschul S.F., Gish W., Miller W., Myers E.W., and Lipman D.J.: Basic local alignment search tool. J Mol Biol 1990; 215: pp. 403-10
4. Arhel N., Genovesio A., Kim K.A., Miko S., Perret E., Olivo-Marin J.C., et al: Quantitative four-dimensional tracking of cytoplasmic and nuclear HIV-1 complexes. Nat Methods 2006; 3: pp. 817-24
5. Azimi F.C., and Lee J.E.: Structural perspectives on HIV-1 Vif and APOBEC3 restriction factor interactions. Protein Sci 2019: pp.
6. Barroso H., Borrego P., Bartolo I., Marcelino J.M., Familia C., Quintas A., et al: Evolutionary and structural features of the C2, V3 and C3 envelope regions underlying the differences in HIV-1 and HIV-2 biology and infection. PLoS One 2011; 6: pp. e14548
7. Beyrer C., Baral S.D., van Griensven F., Goodreau S.M., Chariyalertsak S., Wirtz A.L., et al: Global epidemiology of HIV infection in men who have sex with men. Lancet 2012; 380: pp. 367-77
8. Brandenburg B., and Zhuang X.: Virus trafficking - learning from single-virus tracking. Nat Rev Microbiol 2007; 5: pp. 197-208
9. Buffalo C.Z., Iwamoto Y., Hurley J.H., and Ren X.: How HIV Nef Proteins Hijack Membrane Traffic To Promote Infection. J Virol 2019; 93: pp.
10. Caro-Perez N., Martinez-Rebollar M., Gregori J., Quer J., Gonzalez P., Gambato M., et al: Phylogenetic analysis of an epidemic outbreak of acute hepatitis C in HIV-infected patients by ultra-deep pyrosequencing. J Clin Virol 2017; 92: pp. 42-7
11. Centers for Disease Control R.O.C.T. Statistics of HIV/AIDS 2016. 2018.
12. Centers for Disease Control R.O.C.T. Statistics of HIV/AIDS 2019/11. 2019.
13. Chen F., Xu X.Y., Zhang M., Chen C., Shao H.T., and Shi Y.: Deep sequencing profiles MicroRNAs related to Aspergillus fumigatus infection in lung tissues of mice. J Microbiol Immunol Infect 2019; 52: pp. 90-9
14. Chen Y.J., Huang Y.H., Chuang S.Y., Kao D.Y., Lan Y.C., Yang J.Y., et al: Molecular epidemiology of HIV-1 subtype B, CRF01_AE, and CRF07_BC infection among injection drug users in Taiwan. J Acquir Immune Defic Syndr 2010; 53: pp. 425-39
15. Chen Y.J., Lee C.M., Chen M., Chuang S.Y., Liu H.F., Wong W.W., et al: Molecular epidemiology of HIV-1 infection in Taiwan from 2005 to 2008: further spread of CRF07_BC and emergence of CRF07_BC/subtype B dual infection. J Acquir Immune Defic Syndr 2012; 59: pp. 438-46
16. Chen Y.M., Huang K.L., Jen I., Chen S.C., Liu Y.C., Chuang Y.C., et al: Temporal trends and molecular epidemiology of HIV-1 infection in Taiwan from 1988 to 1998. J Acquir Immune Defic Syndr 2001; 26: pp. 274-82
17. Chen Y.M., Lan Y.C., Lai S.F., Yang J.Y., Tsai S.F., and Kuo S.H.: HIV-1 CRF07_BC infections, injecting drug users, Taiwan. Emerg Infect Dis 2006; 12: pp. 703-5
18. Chojnacki J., and Muller B.: Investigation of HIV-1 assembly and release using modern fluorescence imaging techniques. Traffic 2013; 14: pp. 15-24
19. Coffin J.M.: HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 1995; 267: pp. 483-9
20. Daecke J., Fackler O.T., Dittmar M.T., and Krausslich H.G.: Involvement of clathrin-mediated endocytosis in human immunodeficiency virus type 1 entry. J Virol 2005; 79: pp. 1581-94
21. Dale B.M., McNerney G.P., Hubner W., Huser T.R., and Chen B.K.: Tracking and quantitation of fluorescent HIV during cell-to-cell transmission. Methods 2011; 53: pp. 20-6
22. de Sousa Mascena Veras M.A., Calazans G.J., de Almeida Ribeiro M.C., de Freitas Oliveira C.A., Giovanetti M.R., Facchini R., et al: High HIV Prevalence among Men who have Sex with Men in a Time-Location Sampling Survey, Sao Paulo, Brazil. AIDS Behav 2015; 19: pp. 1589-98
23. Domingo E., Sheldon J., and Perales C.: Viral quasispecies evolution. Microbiol Mol Biol Rev 2012; 76: pp. 159-216
24. Drumright L.N., and Frost S.D.: Sexual networks and the transmission of drug-resistant HIV. Curr Opin Infect Dis 2008; 21: pp. 644-52
25. Eggeling C., Widengren J., Rigler R., and Seidel C.A.: Photobleaching of Fluorescent Dyes under Conditions Used for Single-Molecule Detection: Evidence of Two-Step Photolysis. Anal Chem 1998; 70: pp. 2651-9
26. Ehrnst A.: Challenges in virological diagnosis of HIV -1 transmission from sexual abuse--HIV-1 genetic links are mandatory. Am J Reprod Immunol 2013; 69 Suppl 1: pp. 116-21
27. Feng Y., Chen C.L., Chen T.H., Liang Y.H., Chen H.L., Lin C.Y., et al: Application of next-generation sequencing to study ascitic microbiome in cirrhotic patients with or without spontaneous bacterial peritonitis. J Microbiol Immunol Infect 2015; 48: pp. 504-9
28. Gama A., Martins M.O., and Dias S.: HIV Research with Men who Have Sex with Men (MSM): Advantages and Challenges of Different Methods for Most Appropriately Targeting a Key Population. AIMS Public Health 2017; 4: pp. 221-39
29. Garcia J.V., and Miller A.D.: Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature 1991; 350: pp. 508-11
30. Gios L., Mirandola M., Toskin I., Marcus U., Dudareva-Vizule S., Sherriff N., et al: Bio-behavioural HIV and STI surveillance among men who have sex with men in Europe: the Sialon II protocols. BMC Public Health 2016; 16: pp. 212
31. Gonzalez-Candelas F., Bracho M.A., Wrobel B., and Moya A.: Molecular evolution in court: analysis of a large hepatitis C virus outbreak from an evolving source. BMC Biol 2013; 11: pp. 76
32. Goret J., Baudinet T., Camou F., Issa N., Gaillard P., Wirth G., et al: Identification of Streptococcus sinensis from a patient with endocarditis using MALDI-TOF mass spectrometry, 16S rDNA- and sodA-based phylogeny. J Microbiol Immunol Infect 2019; 52: pp. 507-9
33. Greenwood G.L., White E.W., Page-Shafer K., Bein E., Osmond D.H., Paul J., et al: Correlates of heavy substance use among young gay and bisexual men: The San Francisco Young Men's Health Study. Drug Alcohol Depend 2001; 61: pp. 105-12
34. Gutierrez-Granados S., Cervera L., Godia F., Carrillo J., and Segura M.M.: Development and validation of a quantitation assay for fluorescently tagged HIV-1 virus-like particles. J Virol Methods 2013; 193: pp. 85-95
35. Haaland R.E., Hawkins P.A., Salazar-Gonzalez J., Johnson A., Tichacek A., Karita E., et al: Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog 2009; 5: pp. e1000274
36. Hall T.A.: BioEdit: A user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 1999; 41: pp. 95–8
37. Hall T.A.: BioEdit: A user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. . Nucl Acids Symp Ser 1999; 41: pp. 95–8
38. Harms G.S., Cognet L., Lommerse P.H., Blab G.A., and Schmidt T.: Autofluorescent proteins in single-molecule research: applications to live cell imaging microscopy. Biophys J 2001; 80: pp. 2396-408
39. Hecht R., Bollinger L., Stover J., McGreevey W., Muhib F., Madavo C.E., et al: Critical choices in financing the response to the global HIV/AIDS pandemic. Health Aff (Millwood) 2009; 28: pp. 1591-605
40. HelenBridle. Waterborne Pathogens-Detection Methods and Applications: Academic Press; 2014. 416 p.
41. Helenius A., Kartenbeck J., Simons K., and Fries E.: On the entry of Semliki forest virus into BHK-21 cells. J Cell Biol 1980; 84: pp. 404-20
42. Hemelaar J., Elangovan R., Yun J., Dickson-Tetteh L., Fleminger I., Kirtley S., et al: Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis. Lancet Infect Dis 2019; 19: pp. 143-55
43. Hemelaar J., Gouws E., Ghys P.D., and Osmanov S.: Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004. AIDS 2006; 20: pp. W13-23
44. Hermle J., Anders M., Heuser A.M., and Muller B.: A simple fluorescence based assay for quantification of human immunodeficiency virus particle release. BMC Biotechnol 2010; 10: pp. 32
45. Hess K.L., Crepaz N., Rose C., Purcell D., and Paz-Bailey G.: Trends in Sexual Behavior Among Men Who have Sex with Men (MSM) in High-Income Countries, 1990-2013: A Systematic Review. AIDS Behav 2017; 21: pp. 2811-34
46. Hidaka Y., Ichikawa S., Koyano J., Urao M., Yasuo T., Kimura H., et al: Substance use and sexual behaviours of Japanese men who have sex with men: a nationwide internet survey conducted in Japan. BMC Public Health 2006; 6: pp. 239
47. Hillis D.M., Allard M.W., and Miyamoto M.M.: Analysis of DNA sequence data: phylogenetic inference. Methods Enzymol 1993; 224: pp. 456-87
48. Hohng S., and Ha T.: Near-complete suppression of quantum dot blinking in ambient conditions. J Am Chem Soc 2004; 126: pp. 1324-5
49. Huang S.W., Wang S.F., Cowo A.E., Chen M., Lin Y.T., Hung C.P., et al: Molecular Epidemiology of HIV-1 Infection among Men who Have Sex with Men in Taiwan in 2012. PLoS One 2015; 10: pp. e0128266
50. Jennes W., Kyongo J.K., Vanhommerig E., Camara M., Coppens S., Seydi M., et al: Molecular epidemiology of HIV-1 transmission in a cohort of HIV-1 concordant heterosexual couples from Dakar, Senegal. PLoS One 2012; 7: pp. e37402
51. Jun S., Ke D., Debiec K., Zhao G., Meng X., Ambrose Z., et al: Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Structure 2011; 19: pp. 1573-81
52. Kaye M., Chibo D., and Birch C.: Comparison of Bayesian and maximum-likelihood phylogenetic approaches in two legal cases involving accusations of transmission of HIV. AIDS Res Hum Retroviruses 2009; 25: pp. 741-8
53. Keele B.F., Giorgi E.E., Salazar-Gonzalez J.F., Decker J.M., Pham K.T., Salazar M.G., et al: Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 2008; 105: pp. 7552-7
54. Kelly B.C.: Conceptions of risk in the lives of club drug-using youth. Subst Use Misuse 2005; 40: pp. 1443-59
55. Ko N.Y., Koe S., Lee H.C., Yen C.F., Ko W.C., and Hsu S.T.: Online sex-seeking, substance use, and risky behaviors in Taiwan: results from the 2010 Asia Internet MSM Sex Survey. Arch Sex Behav 2012; 41: pp. 1273-82
56. Ko N.Y., Tseng P.C., Huang Y.C., Chen Y.C., and Hsu S.T.: Seeking sex partners through the internet and mobile phone applications among men who have sex with men in Taiwan. AIDS Care 2016; 28: pp. 927-31
57. Kurnaeva M.A., Sheval E.V., Musinova Y.R., and Vassetzky Y.S.: Tat basic domain: A "Swiss army knife" of HIV-1 Tat? Rev Med Virol 2019; 29: pp. e2031
58. Lan Y.C., Elbeik T., Dileanis J., Ng V., Chen Y.J., Leu H.S., et al: Molecular epidemiology of HIV-1 subtypes and drug resistant strains in Taiwan. J Med Virol 2008; 80: pp. 183-91
59. Lau K.A., and Wong J.J.: Current Trends of HIV Recombination Worldwide. Infect Dis Rep 2013; 5: pp. e4
60. Lee S.J., Galanter M., Dermatis H., and McDowell D.: Circuit parties and patterns of drug use in a subset of gay men. J Addict Dis 2003; 22: pp. 47-60
61. Leitner T., and Romero-Severson E.: Phylogenetic patterns recover known HIV epidemiological relationships and reveal common transmission of multiple variants. Nat Microbiol 2018; 3: pp. 983-8
62. Lemey P., Derdelinckx I., Rambaut A., Van Laethem K., Dumont S., Vermeulen S., et al: Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain. J Virol 2005; 79: pp. 11981-9
63. Lemey P., Kosakovsky Pond S.L., Drummond A.J., Pybus O.G., Shapiro B., Barroso H., et al: Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics. PLoS Comput Biol 2007; 3: pp. e29
64. Lemey P., Suchard M., and Rambaut A.: Reconstructing the initial global spread of a human influenza pandemic: A Bayesian spatial-temporal model for the global spread of H1N1pdm. PLoS Curr 2009; 1: pp. RRN1031
65. Lewis F., Hughes G.J., Rambaut A., Pozniak A., and Leigh Brown A.J.: Episodic sexual transmission of HIV revealed by molecular phylodynamics. PLoS Med 2008; 5: pp. e50
66. Liau A., Millett G., and Marks G.: Meta-analytic examination of online sex-seeking and sexual risk behavior among men who have sex with men. Sex Transm Dis 2006; 33: pp. 576-84
67. Lin G.L., Lu C.Y., Chen J.M., Lee P.I., Ho S.Y., Weng K.C., et al: Molecular epidemiology and clinical features of adenovirus infection in Taiwanese children, 2014. J Microbiol Immunol Infect 2019; 52: pp. 215-24
68. Lin Y.T., Lan Y.C., Chen Y.J., Huang Y.H., Lee C.M., Liu T.T., et al: Molecular epidemiology of HIV-1 infection and full-length genomic analysis of circulating recombinant form 07_BC strains from injection drug users in Taiwan. J Infect Dis 2007; 195: pp. 1283-93
69. Liu W.D., Tsai W.C., Hsu W.T., Shih M.C., Chen M.Y., Sun H.Y., et al: Impact of initiation of combination antiretroviral therapy according to the WHO recommendations on the survival of HIV-positive patients in Taiwan. J Microbiol Immunol Infect 2019: pp.
70. Magnani R., Sabin K., Saidel T., and Heckathorn D.: Review of sampling hard-to-reach and hidden populations for HIV surveillance. AIDS 2005; 19 Suppl 2: pp. S67-72
71. Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., and Weiner D.B.: Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr. J Virol 1997; 71: pp. 6339-47
72. Margulies M., Egholm M., Altman W.E., Attiya S., Bader J.S., Bemben L.A., et al: Genome sequencing in microfabricated high-density picolitre reactors. Nature 2005; 437: pp. 376-80
73. Maxwell J.C.: Party drugs: properties, prevalence, patterns, and problems. Subst Use Misuse 2005; 40: pp. 1203-40
74. McCarthy A.: Third generation DNA sequencing: pacific biosciences' single molecule real time technology. Chem Biol 2010; 17: pp. 675-6
75. McGovern S.L., Caselli E., Grigorieff N., and Shoichet B.K.: A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J Med Chem 2002; 45: pp. 1712-22
76. Mehrbod P., Ande S.R., Alizadeh J., Rahimizadeh S., Shariati A., Malek H., et al: The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections. Virulence 2019; 10: pp. 376-413
77. Melendez-Torres G.J., Nye E., and Bonell C.: Internet sex-seeking is inconsistently linked with sexual risk in men who have sex with men: systematic review of within-subjects comparisons. Sex Health 2015; 12: pp. 183-7
78. Metzker M.L.: Sequencing technologies - the next generation. Nat Rev Genet 2010; 11: pp. 31-46
79. Metzker M.L., Mindell D.P., Liu X.M., Ptak R.G., Gibbs R.A., and Hillis D.M.: Molecular evidence of HIV-1 transmission in a criminal case. Proc Natl Acad Sci U S A 2002; 99: pp. 14292-7
80. Mills S., Saidel T., Magnani R., and Brown T.: Surveillance and modelling of HIV, STI, and risk behaviours in concentrated HIV epidemics. Sex Transm Infect 2004; 80 Suppl 2: pp. ii57-62
81. Miyauchi K., Kim Y., Latinovic O., Morozov V., and Melikyan G.B.: HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 2009; 137: pp. 433-44
82. Mouzakis K.D., Lang A.L., Vander Meulen K.A., Easterday P.D., and Butcher S.E.: HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome. Nucleic Acids Res 2013; 41: pp. 1901-13
83. Ou C.Y., Ciesielski C.A., Myers G., Bandea C.I., Luo C.C., Korber B.T., et al: Molecular epidemiology of HIV transmission in a dental practice. Science 1992; 256: pp. 1165-71
84. Ouellet D.L., Plante I., Landry P., Barat C., Janelle M.E., Flamand L., et al: Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. Nucleic Acids Res 2008; 36: pp. 2353-65
85. Oyomopito R.A., Chen Y.J., Sungkanuparph S., Kantor R., Merati T., Yam W.C., et al: Risk group characteristics and viral transmission clusters in South-East Asian patients infected with human immunodeficiency virus-1 (HIV-1) circulating recombinant form (CRF) 01_AE and subtype B. Kaohsiung J Med Sci 2015; 31: pp. 445-53
86. Patterson S.E., Milloy M.J., Ogilvie G., Greene S., Nicholson V., Vonn M., et al: The impact of criminalization of HIV non-disclosure on the healthcare engagement of women living with HIV in Canada: a comprehensive review of the evidence. J Int AIDS Soc 2015; 18: pp. 20572
87. Patterson T.L., Semple S.J., Zians J.K., and Strathdee S.A.: Methamphetamine-using HIV-positive men who have sex with men: correlates of polydrug use. J Urban Health 2005; 82: pp. i120-6
88. Redoschi B.R.L., Zucchi E.M., Barros C., and Paiva V.S.F.: Routine HIV testing in men who have sex with men: from risk to prevention. Cad Saude Publica 2017; 33: pp. e00014716
89. Romero-Severson E., Skar H., Bulla I., Albert J., and Leitner T.: Timing and order of transmission events is not directly reflected in a pathogen phylogeny. Mol Biol Evol 2014; 31: pp. 2472-82
90. Romero-Severson E.O., Bulla I., and Leitner T.: Phylogenetically resolving epidemiologic linkage. Proc Natl Acad Sci U S A 2016; 113: pp. 2690-5
91. Roy D., Mandal S., De C.K., Kumar K., and Mandal P.K.: Nearly suppressed photoluminescence blinking of small-sized, blue-green-orange-red emitting single CdSe-based core/gradient alloy shell/shell quantum dots: correlation between truncation time and photoluminescence quantum yield. Phys Chem Chem Phys 2018; 20: pp. 10332-44
92. Rusch M., Lampinen T.M., Schilder A., and Hogg R.S.: Unprotected anal intercourse associated with recreational drug use among young men who have sex with men depends on partner type and intercourse role. Sex Transm Dis 2004; 31: pp. 492-8
93. Sajantila A.: Molecular clocks ticking in the court room. Investig Genet 2014; 5: pp. 4
94. Sandfort T.G.M., Knox J.R., Alcala C., El-Bassel N., Kuo I., and Smith L.R.: Substance Use and HIV Risk Among Men Who Have Sex With Men in Africa: A Systematic Review. J Acquir Immune Defic Syndr 2017; 76: pp. e34-e46
95. Scaduto D.I., Brown J.M., Haaland W.C., Zwickl D.J., Hillis D.M., and Metzker M.L.: Source identification in two criminal cases using phylogenetic analysis of HIV-1 DNA sequences. Proc Natl Acad Sci U S A 2010; 107: pp. 21242-7
96. Sharp P.M., and Hahn B.H.: The evolution of HIV-1 and the origin of AIDS. Philos Trans R Soc Lond B Biol Sci 2010; 365: pp. 2487-94
97. Smith D.K., Pals S.L., Herbst J.H., Shinde S., and Carey J.W.: Development of a clinical screening index predictive of incident HIV infection among men who have sex with men in the United States. J Acquir Immune Defic Syndr 2012; 60: pp. 421-7
98. Suguimoto S.P., Techasrivichien T., Musumari P.M., El-saaidi C., Lukhele B.W., Ono-Kihara M., et al: Changing patterns of HIV epidemic in 30 years in East Asia. Curr HIV/AIDS Rep 2014; 11: pp. 134-45
99. Sun W., Reyes-Serratos E., Barilla D., Santos J.R.L., Bujold M., Graves S., et al: Mathematical determination of the HIV-1 matrix shell structure and its impact on the biology of HIV-1. PLoS One 2019; 14: pp. e0224965
100. Tamura K., Stecher G., Peterson D., Filipski A., and Kumar S.: MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol 2013; 30: pp. 2725-9
101. Thomson M.M., Perez-Alvarez L., and Najera R.: Molecular epidemiology of HIV-1 genetic forms and its significance for vaccine development and therapy. Lancet Infect Dis 2002; 2: pp. 461-71
102. Uchil P.D., and Mothes W.: HIV Entry Revisited. Cell 2009; 137: pp. 402-4
103. UNAIDS: 2019 UNAIDS data. Available from: https://www.unaids.org/en/resources/documents/2019/2019-UNAIDS-data.
104. UNAIDS: Criminalisation of HIV Non-Disclosure, Exposure and Transmission: Background and Current Landscape.
105. van Griensven F., de Lind van Wijngaarden J.W., Baral S., and Grulich A.: The global epidemic of HIV infection among men who have sex with men. Curr Opin HIV AIDS 2009; 4: pp. 300-7
106. van Sark W.G.J.H.M., Frederix P.L.T.M., Bol A.A., Gerritsen H.C., and Meijerink A.: Blueing, bleaching, and blinking of single CdSe/ZnS quantum dots. Chemphyschem 2002; 3: pp. 871-9
107. Vandamme A.M., and Pybus O.G.: Viral phylogeny in court: the unusual case of the Valencian anesthetist. BMC Biol 2013; 11: pp. 83
108. Vieweger M., Goicochea N., Koh E.S., and Dragnea B.: Photothermal imaging and measurement of protein shell stoichiometry of single HIV-1 Gag virus-like nanoparticles. ACS Nano 2011; 5: pp. 7324-33
109. Volz E.M., Ionides E., Romero-Severson E.O., Brandt M.G., Mokotoff E., and Koopman J.S.: HIV-1 transmission during early infection in men who have sex with men: a phylodynamic analysis. PLoS Med 2013; 10: pp. e1001568
110. Vosburgh H.W., Mansergh G., Sullivan P.S., and Purcell D.W.: A review of the literature on event-level substance use and sexual risk behavior among men who have sex with men. AIDS Behav 2012; 16: pp. 1394-410
111. Vrancken B., Rambaut A., Suchard M.A., Drummond A., Baele G., Derdelinckx I., et al: The genealogical population dynamics of HIV-1 in a large transmission chain: bridging within and among host evolutionary rates. PLoS Comput Biol 2014; 10: pp. e1003505
112. Wang N., Tang Z., Li Y., Xie P., and Shao Y.: Molecular linkage tracing of HIV-1 transmission events in seroconcordant couples in Guangxi Province, Southeastern China. Springerplus 2016; 5: pp. 2015
113. Wei M., Guan Q., Liang H., Chen J., Chen Z., Hei F., et al: Simple subtyping assay for human immunodeficiency virus type 1 subtypes B, C, CRF01-AE, CRF07-BC, and CRF08-BC. J Clin Microbiol 2004; 42: pp. 4261-7
114. WHO: Summary of the global HIV epidemic, 2018. Available from: https://www.who.int/hiv/data/en/.
115. Yamaguchi J., McArthur C., Vallari A., Sthreshley L., Cloherty G.A., Berg M.G., et al: Complete genome sequence of CG-0018a-01 establishes HIV-1 subtype L. J Acquir Immune Defic Syndr 2019: pp.
116. Yang C., Zhang G., Feng L., Li B., Li Z., Chen R., et al: Suppressing the photobleaching and photoluminescence intermittency of single near-infrared CdSeTe/ZnS quantum dots with p-phenylenediamine. Opt Express 2018; 26: pp. 11889-902
117. York T.L., Durrett R.T., Tanksley S., and Nielsen R.: Bayesian and maximum likelihood estimation of genetic maps. Genet Res 2005; 85: pp. 159-68
118. Yuan G., Gomez D.E., Kirkwood N., Boldt K., and Mulvaney P.: Two Mechanisms Determine Quantum Dot Blinking. ACS Nano 2018; 12: pp. 3397-405
119. Zhang Y., Ke X., Zheng Z., Zhang C., Zhang Z., Zhang F., et al: Encapsulating quantum dots into enveloped virus in living cells for tracking virus infection. ACS Nano 2013; 7: pp. 3896-904