{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:17:59Z","timestamp":1792441079147,"version":"4.5.0"},"reference-count":217,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["13FH242PX6"],"award-info":[{"award-number":["13FH242PX6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Different mechanisms mediate the toxicity of RNA. Genomic retroviral mRNA hijacks infected host cell factors to enable virus replication. The viral genomic RNA of the human immunodeficiency virus (HIV) encompasses nine genes encoding in less than 10 kb all proteins needed for replication in susceptible host cells. To do so, the genomic RNA undergoes complex alternative splicing to facilitate the synthesis of the structural, accessory, and regulatory proteins. However, HIV strongly relies on the host cell machinery recruiting cellular factors to complete its replication cycle. Antiretroviral therapy (ART) targets different steps in the cycle, preventing disease progression to the acquired immunodeficiency syndrome (AIDS). The comprehension of the host immune system interaction with the virus has fostered the development of a variety of vaccine platforms. Despite encouraging provisional results in vaccine trials, no effective vaccine has been developed, yet. However, novel promising vaccine platforms are currently under investigation.<\/jats:p>","DOI":"10.3390\/toxins14020138","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T20:58:03Z","timestamp":1644872283000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6808-056X","authenticated-orcid":false,"given":"Yasemin","family":"van Heuvel","sequence":"first","affiliation":[{"name":"Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH K\u00f6ln\u2014University of Applied Sciences, Chempark Leverkusen, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany"},{"name":"Institute of Technical Chemistry, Leibniz University Hannover, Callinstra\u00dfe 3-9, 30167 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-1342","authenticated-orcid":false,"given":"Stefanie","family":"Schatz","sequence":"additional","affiliation":[{"name":"Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH K\u00f6ln\u2014University of Applied Sciences, Chempark Leverkusen, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany"},{"name":"Institute of Technical Chemistry, Leibniz University Hannover, Callinstra\u00dfe 3-9, 30167 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1576-0160","authenticated-orcid":false,"given":"Jamila Franca","family":"Rosengarten","sequence":"additional","affiliation":[{"name":"Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH K\u00f6ln\u2014University of Applied Sciences, Chempark Leverkusen, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany"},{"name":"Institute of Technical Chemistry, Leibniz University Hannover, Callinstra\u00dfe 3-9, 30167 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-786X","authenticated-orcid":false,"given":"J\u00f6rn","family":"Stitz","sequence":"additional","affiliation":[{"name":"Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH K\u00f6ln\u2014University of Applied Sciences, Chempark Leverkusen, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180017","DOI":"10.1038\/sdata.2018.17","article-title":"Epidemiological characteristics of human-infective RNA viruses","volume":"5","author":"Woolhouse","year":"2018","journal-title":"Sci. Data"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, F., Chase-Topping, M., Guo, C.G., van Bunnik, B.A.D., Brierley, L., and Woolhouse, M.E.J. (2020). Global discovery of human-infective RNA viruses: A modelling analysis. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1009079"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tarantola, A. (2017). Four thousand years of concepts relating to rabies in animals and humans, its prevention and its cure. Trop. Med. Infect. Dis., 2.","DOI":"10.3390\/tropicalmed2020005"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s10072-016-2720-9","article-title":"Poliomyelitis in Ancient Egypt?","volume":"38","author":"Galassi","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"584","DOI":"10.4269\/ajtmh.2012.11-0770","article-title":"Review: The history of dengue outbreaks in the Americas","volume":"87","author":"Dick","year":"2012","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_6","unstructured":"Fields, B.N., Knipe, D.M., and Howley, P.M. (1990). Fields Virology, Wolters Kluwer Health\/Lippincott Williams & Wilkins. [5th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.mpmed.2021.07.011","article-title":"The epidemiology of emerging infectious diseases and pandemics","volume":"49","year":"2021","journal-title":"Medicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/326435a0","article-title":"The chronology of AIDS research","volume":"326","year":"1987","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.6189183","article-title":"Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)","volume":"220","author":"Chermann","year":"1983","journal-title":"Science."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Murphy, K., and Weaver, C. (2018). Das erworbene Immunschw\u00e4chesyndrom (AIDS). Janeway Immunologie, Springer-Spektrum.","DOI":"10.1007\/978-3-662-56004-4"},{"key":"ref_11","unstructured":"(2021, October 19). WHO HIV\/AIDS. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hiv-aids."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"a006965","DOI":"10.1101\/cshperspect.a006965","article-title":"HIV transmission","volume":"2","author":"Shaw","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"a007161","DOI":"10.1101\/cshperspect.a007161","article-title":"HIV-1 antiretroviral drug therapy","volume":"2","author":"Arts","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11537","DOI":"10.1073\/pnas.1605739113","article-title":"Concomitant emergence of the antisense protein gene of HIV-1 and of the pandemic","volume":"113","author":"Cassan","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.virol.2018.01.011","article-title":"Behind the scenes of HIV-1 replication: Alternative splicing as the dependency factor on the quiet","volume":"516","author":"Sertznig","year":"2018","journal-title":"Virology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1126\/science.3347840","article-title":"Human Immunodeficiency Virus May Encode a Novel Protein on the Genomic DNA Plus Strand","volume":"239","author":"Miller","year":"1988","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s13365-014-0271-5","article-title":"HIV-1 transcriptional regulation in the central nervous system and implications for HIV cure research","volume":"21","author":"Churchill","year":"2015","journal-title":"J. Neurovirol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Barboric, M., and Matija Peterlin, B. (2005). A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional elongation. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030076"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mbondji-Wonje, C., Dong, M., Zhao, J., Wang, X., Nanfack, A., Ragupathy, V., Sanchez, A.M., Denny, T.N., and Hewlett, I. (2020). Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-70083-1"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kirchhoff, F. (2013). HIV Life Cycle: Overview. Encyclopedia of AIDS, Springer.","DOI":"10.1007\/978-1-4614-9610-6_60-1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/sj.cr.7290370","article-title":"Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions","volume":"15","author":"Li","year":"2005","journal-title":"Cell Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7742","DOI":"10.1128\/JVI.00392-07","article-title":"The TAR Hairpin of Human Immunodeficiency Virus Type 1 Can Be Deleted When Not Required for Tat-Mediated Activation of Transcription","volume":"81","author":"Das","year":"2007","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000445852","article-title":"Human Immunodeficiency Virus (HIV)","volume":"43","author":"Seitz","year":"2016","journal-title":"Transfus. Med. Hemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40875","DOI":"10.1074\/jbc.R112.416925","article-title":"The restriction factors of human immunodeficiency virus","volume":"287","author":"Harris","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"a006940","DOI":"10.1101\/cshperspect.a006940","article-title":"HIV restriction factors and mechanisms of evasion","volume":"2","author":"Malim","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_26","first-page":"14451","article-title":"IFITM proteins inhibit HIV-1 protein synthesis","volume":"8","author":"Lee","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"559792","DOI":"10.3389\/fmicb.2020.559792","article-title":"From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1","volume":"11","author":"Ramdas","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.chom.2007.08.001","article-title":"An Interferon-\u03b1-Induced Tethering Mechanism Inhibits HIV-1 and Ebola Virus Particle Release but Is Counteracted by the HIV-1 Vpu Protein","volume":"2","author":"Neil","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1371\/journal.ppat.1003299","article-title":"Vpu Binds Directly to Tetherin and Displaces It from Nascent Virions","volume":"9","author":"Mcnatt","year":"2013","journal-title":"PLoS Pathog."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1073\/pnas.0509996103","article-title":"Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5\u03b1 restriction factor","volume":"103","author":"Stremlau","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jmbi.1998.2354","article-title":"Structural biology of HIV 1 1Edited by P. E. Wright","volume":"285","author":"Turner","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Burnie, J., and Guzzo, C. (2019). The incorporation of host proteins into the external HIV-1 envelope. Viruses, 11.","DOI":"10.3390\/v11010085"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nature04817","article-title":"Distribution and three-dimensional structure of AIDS virus envelope spikes","volume":"441","author":"Zhu","year":"2006","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/nsmb785","article-title":"The stoichiometry of Gag protein in HIV-1","volume":"11","author":"Briggs","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_35","unstructured":"Goodsell, D.S. (2021, September 29). Viral Zone Expasy. Available online: https:\/\/viralzone.expasy.org\/5182."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nrmicro2747","article-title":"The structural biology of HIV-1: Mechanistic and therapeutic insights","volume":"10","author":"Engelman","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1126\/science.aae0474","article-title":"Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody","volume":"352","author":"Kong","year":"2016","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/31405","article-title":"Structure of an HIV gp 120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody","volume":"393","author":"Kwong","year":"1998","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S0005-2736(03)00161-5","article-title":"The HIV Env-mediated fusion reaction","volume":"1614","author":"Gallo","year":"2003","journal-title":"Biochim. et Biophys. Acta-Biomembr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.cell.2021.01.025","article-title":"Cone-shaped HIV-1 capsids are transported through intact nuclear pores","volume":"184","author":"Zila","year":"2021","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41564-020-0735-8","article-title":"Nuclear pore blockade reveals that HIV-1 completes reverse transcription and uncoating in the nucleus","volume":"5","author":"Dharan","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1073\/pnas.1920631117","article-title":"HIV-1 uncoats in the nucleus near sites of integration","volume":"117","author":"Burdick","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e64776","DOI":"10.7554\/eLife.64776","article-title":"Hiv-1 uncoating by release of viral cdna from capsid-like structures in the nucleus of infected cells","volume":"10","author":"Zila","year":"2021","journal-title":"Elife"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/1742-4690-5-115","article-title":"Human immunodeficiency virus type-1 reverse transcriptase exists as post-translationally modified forms in virions and cells","volume":"5","author":"Davis","year":"2008","journal-title":"Retrovirology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1128\/MMBR.00012-09","article-title":"The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination","volume":"73","author":"Telesnitsky","year":"2009","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cell.2013.09.044","article-title":"An Integrated Overview of HIV-1 Latency","volume":"155","author":"Ruelas","year":"2013","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"a006890","DOI":"10.1101\/cshperspect.a006890","article-title":"HIV DNA integration","volume":"2","author":"Craigie","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"965","DOI":"10.2174\/1568026043388547","article-title":"Structure and Function of HIV-1 Integrase","volume":"4","author":"Chiu","year":"2004","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1177\/095632029700800601","article-title":"HIV-1 integrase as a target for antiviral drugs","volume":"8","author":"Pommier","year":"1997","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"a006916","DOI":"10.1101\/cshperspect.a006916","article-title":"Transcriptional and Posttranscriptional Regulation of HIV-1 Gene Expression","volume":"2","author":"Karn","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dutilleul, A., Rodari, A., and Van Lint, C. (2020). Depicting HIV-1 Transcriptional Mechanisms: A Summary of What We Know. Viruses, 12.","DOI":"10.3390\/v12121385"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Verdikt, R., Hernalsteens, O., and Van Lint, C. (2021). Epigenetic Mechanisms of HIV-1 Persistence. Vaccines, 9.","DOI":"10.3390\/vaccines9050514"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shukla, A., Ramirez, N.G.P., and D\u2019Orso, I. (2020). HIV-1 Proviral Transcription and Latency in the New Era. Viruses, 12.","DOI":"10.3390\/v12050555"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/1873-3468.14033","article-title":"AP-1 and NF-\u03baB synergize to transcriptionally activate latent HIV upon T-cell receptor activation","volume":"595","author":"Hokello","year":"2021","journal-title":"FEBS Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13378","DOI":"10.1073\/pnas.1616627113","article-title":"Transcriptional start site heterogeneity modulates the structure and function of the HIV-1 genome","volume":"113","author":"Kharytonchyk","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1101\/gad.335679.119","article-title":"Structure and mechanism of the RNA polymerase II transcription machinery","volume":"34","author":"Schier","year":"2020","journal-title":"Genes Dev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"681865","DOI":"10.3389\/fmolb.2021.681865","article-title":"Regulation of Eukaryotic RNAPs Activities by Phosphorylation","volume":"8","author":"Campos","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7527","DOI":"10.1093\/nar\/gkw585","article-title":"Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb","volume":"44","author":"Quaresma","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4910","DOI":"10.1128\/jvi.65.9.4910-4918.1991","article-title":"Transcriptional elongation by purified RNA polymerase II is blocked at the trans-activation-responsive region of human immunodeficiency virus type 1 in vitro","volume":"65","author":"Bengal","year":"1991","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/330489a0","article-title":"Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product","volume":"330","author":"Kao","year":"1987","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.celrep.2013.11.003","article-title":"Transcription factors mediate the enzymatic disassembly of promoter-bound 7SK snRNP to locally recruit P-TEFb for transcription elongation","volume":"5","author":"McNamara","year":"2013","journal-title":"Cell Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/21541264.2017.1281864","article-title":"P-TEFb: Finding its ways to release promoter-proximally paused RNA polymerase II","volume":"9","author":"Li","year":"2018","journal-title":"Transcription"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1093\/nar\/gkm063","article-title":"Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription","volume":"35","author":"Barboric","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1038\/s41467-021-24462-5","article-title":"Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting","volume":"12","author":"Tantale","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12977-020-00533-1","article-title":"Dynamic nanopore long-read sequencing analysis of HIV-1 splicing events during the early steps of infection","volume":"17","author":"Goudey","year":"2020","journal-title":"Retrovirology"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Emery, A., and Swanstrom, R. (2021). HIV-1: To Splice or Not to Splice, That Is the Question. Viruses, 13.","DOI":"10.20944\/preprints202101.0114.v1"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/nar\/gki185","article-title":"Splicing of human immunodeficiency virus RNA is position-dependent suggesting sequential removal of introns from the 5\u2032 end","volume":"33","author":"Bohne","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nrmicro1210","article-title":"How retroviruses select their genomes","volume":"3","author":"Summers","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10920","DOI":"10.1038\/s41598-021-90427-9","article-title":"Influence of the 5\u2032-terminal sequences on the 5\u2032-UTR structure of HIV-1 genomic RNA","volume":"11","author":"Obayashi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1261\/rna.073650.119","article-title":"HIV-1 spliced RNAs display transcription start site bias","volume":"26","author":"Esquiaqui","year":"2020","journal-title":"RNA"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Toro-Ascuy, D., Rojas-Araya, B., Valiente-Echeverr\u00eda, F., and Soto-Rifo, R. (2016). Interactions between the HIV-1 unspliced mRNA and host mRNA decay machineries. Viruses, 8.","DOI":"10.3390\/v8110320"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"170270","DOI":"10.1098\/rsob.170270","article-title":"Surveillance-ready transcription: Nuclear RNA decay as a default fate","volume":"8","author":"Bresson","year":"2018","journal-title":"Open Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1261\/rna.038182.113","article-title":"Stable assembly of HIV-1 export complexes occurs cotranscriptionally","volume":"20","author":"Nawroth","year":"2014","journal-title":"RNA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.chom.2008.04.008","article-title":"HIV-1 Accessory Proteins-Ensuring Viral Survival in a Hostile Environment","volume":"3","author":"Malim","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev-virology-101416-041654","article-title":"Making Sense of Multifunctional Proteins: Human Immunodeficiency Virus Type 1 Accessory and Regulatory Proteins and Connections to Transcription","volume":"4","author":"Faust","year":"2017","journal-title":"Annu. Rev. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1128\/MMBR.00065-15","article-title":"HIV Genome-Wide Protein Associations: A Review of 30 Years of Research","volume":"80","author":"Li","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/331280a0","article-title":"Characterization of ribosomal frameshifting in HIV-1 gag-pol expression","volume":"331","author":"Jacks","year":"1988","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Murphy, R.E., and Saad, J.S. (2020). The interplay between HIV-1 Gag binding to the plasma membrane and Env incorporation. Viruses, 12.","DOI":"10.3390\/v12050548"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1126\/science.aaz7959","article-title":"Structural basis for transcriptional start site control of HIV-1 RNA fate","volume":"368","author":"Brown","year":"2020","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e2112475118","DOI":"10.1073\/pnas.2112475118","article-title":"5\u2032-Cap sequestration is an essential determinant of HIV-1 genome packaging","volume":"118","author":"Ding","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Mouhand, A., Pasi, M., Catala, M., Zargarian, L., Belfetmi, A., Barraud, P., Mauffret, O., and Tisn\u00e9, C. (2020). Overview of the nucleic-acid binding properties of the HIV-1 nucleocapsid protein in its different maturation states. Viruses, 12.","DOI":"10.3390\/v12101109"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"16480","DOI":"10.1074\/jbc.RA119.010580","article-title":"Nucleic acid\u2013induced dimerization of HIV-1 Gag protein","volume":"294","author":"Zhao","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14391","DOI":"10.1074\/jbc.RA120.014835","article-title":"HIV-1 Gag protein with or without p6 specifically dimerizes on the viral RNA packaging signal","volume":"295","author":"Sarni","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.str.2005.07.010","article-title":"Retroviral matrix domains share electrostatic homology: Models for membrane binding function throughout the viral life cycle","volume":"13","author":"Murray","year":"2005","journal-title":"Structure"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12196","DOI":"10.1128\/JVI.01197-09","article-title":"Analysis of Human Immunodeficiency Virus Type 1 Matrix Binding to Membranes and Nucleic Acids","volume":"83","author":"Alfadhli","year":"2009","journal-title":"J. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1016\/j.jmb.2018.04.042","article-title":"HIV-1 Matrix Protein Interactions with tRNA: Implications for Membrane Targeting","volume":"430","author":"Gaines","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jmb.2010.11.051","article-title":"HIV-1 Gag extension: Conformational changes require simultaneous interaction with membrane and nucleic acid","volume":"406","author":"Datta","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chen, S., Xu, J., Liu, M., Rao, A.L.N., Zandi, R., Gill, S.S., and Mohideen, U. (2020). Investigation of HIV-1 Gag binding with RNAs and lipids using Atomic Force Microscopy. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228036"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6098","DOI":"10.1111\/j.1742-4658.2009.07313.x","article-title":"The capsid protein of human immunodeficiency virus: Intersubunit interactions during virus assembly","volume":"276","author":"Mateu","year":"2009","journal-title":"FEBS J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1128\/jvi.69.5.2759-2764.1995","article-title":"The p6gag domain of human immunodeficiency virus type 1 is sufficient for the incorporation of Vpr into heterologous viral particles","volume":"69","author":"Kondo","year":"1995","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1042\/BST20180019","article-title":"Inside job: How the ESCRTs release HIV-1 from infected cells","volume":"46","author":"Hurley","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kleinpeter, A.B., and Freed, E.O. (2020). HIV-1 maturation: Lessons learned from inhibitors. Viruses, 12.","DOI":"10.3390\/v12090940"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.coviro.2019.05.004","article-title":"Maturation of retroviruses","volume":"36","author":"Pornillos","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.1016\/j.bpj.2021.09.017","article-title":"Stability and conformation of the dimeric HIV-1 genomic RNA 5\u2032UTR","volume":"120","author":"Blakemore","year":"2021","journal-title":"Biophys. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1128\/JVI.78.2.1026-1031.2004","article-title":"Regulation of Human Immunodeficiency Virus Type 1 Env-Mediated Membrane Fusion by Viral Protease Activity","volume":"78","author":"Murakami","year":"2004","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Elcheva, I.A., and Spiegelman, V.S. (2020). The role of cis-and trans-acting rna regulatory elements in leukemia. Cancers, 12.","DOI":"10.3390\/cancers12123854"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.neuro.29.051605.113014","article-title":"RNA-mediated neuromuscular disorders","volume":"29","author":"Ranum","year":"2006","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/nature05977","article-title":"Expandable DNA repeats and human disease","volume":"447","author":"Mirkin","year":"2007","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Heinz, A., Nabariya, D.K., and Krauss, S. (2021). Huntingtin and Its Role in Mechanisms of RNA-Mediated Toxicity. Toxins, 13.","DOI":"10.3390\/toxins13070487"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Kim, W., Kim, D.Y., and Lee, K.H. (2021). Rna-binding proteins and the complex pathophysiology of als. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052598"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.molcel.2019.01.017","article-title":"System-wide Profiling of RNA-Binding Proteins Uncovers Key Regulators of Virus Infection","volume":"74","author":"Noerenberg","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/1742-4690-9-59","article-title":"Opening of the TAR hairpin in the HIV-1 genome causes aberrant RNA dimerization and packaging","volume":"9","author":"Das","year":"2012","journal-title":"Retrovirology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4161\/rna.9.1.18178","article-title":"The HIV-1 Rev response element","volume":"9","author":"Fernandes","year":"2012","journal-title":"RNA Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fcimb.2020.00061","article-title":"HIV-1 Tat: Role in Bystander Toxicity","volume":"10","author":"Ajasin","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.1074\/jbc.M006892200","article-title":"A Role of RNA Helicase A in cis-Acting Transactivation Response Element-mediated Transcriptional Regulation of Human Immunodeficiency Virus Type 1","volume":"276","author":"Fujii","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fneur.2019.00285","article-title":"Release of Soluble Insulin Receptor From Neurons by Cerebrospinal Fluid From Patients With Neurocognitive Dysfunction and HIV Infection","volume":"10","author":"Gerena","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-pathol-011110-130254","article-title":"Pathogenic Mechanisms of HIV Disease","volume":"6","author":"Moir","year":"2011","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"15035","DOI":"10.1038\/nrdp.2015.35","article-title":"HIV infection","volume":"1","author":"Deeks","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Cesarman, E., Damania, B., Krown, S.E., Martin, J., Bower, M., and Whitby, D. (2019). Kaposi sarcoma. Nat. Rev. Dis. Prim., 5.","DOI":"10.1038\/s41572-019-0060-9"},{"key":"ref_110","unstructured":"Justiz Vaillant, A.A., and Naik, R. (2021, October 21). HIV-1 Associated Opportunistic Infections, Available online: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30969609."},{"key":"ref_111","unstructured":"U.S. Department of Health & Human Services Global Statistics (2021, October 21). Available online: https:\/\/www.hiv.gov\/hiv-basics\/overview\/data-and-trends\/global-statistics."},{"key":"ref_112","first-page":"2789","article-title":"Combination antiretroviral therapy for HIV infection","volume":"57","author":"Maenza","year":"1998","journal-title":"Am. Fam. Physician"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1177\/0091270007308034","article-title":"Therapeutic review: Antiretroviral drugs","volume":"47","author":"Warnke","year":"2007","journal-title":"J. Clin. Pharmacol."},{"key":"ref_114","unstructured":"Panel on Antiretroviral Guidelines for Adults and Adolescents (2021, October 25). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, Dep. Heal. Hum. Serv., Available online: https:\/\/clinicalinfo.hiv.gov\/sites\/default\/files\/guidelines\/archive\/AdultandAdolescentGL_2021_08_16.pdf."},{"key":"ref_115","unstructured":"U.S. Department of Health & Human Services FDA-Approved HIV Medicines (2021, October 21). Available online: https:\/\/hivinfo.nih.gov\/understanding-hiv\/fact-sheets\/fda-approved-hiv-medicines."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"112819","DOI":"10.1016\/j.ejmech.2020.112819","article-title":"Advances of CCR5 antagonists: From small molecules to macromolecules","volume":"208","author":"Qi","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/ajhp\/61.12.1242","article-title":"Enfuvirtide: First fusion inhibitor for treatment of HIV infection","volume":"61","author":"Jamjian","year":"2004","journal-title":"Am. J. Health Pharm."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1021\/acs.jmedchem.7b01337","article-title":"Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir","volume":"61","author":"Meanwell","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e00110","DOI":"10.1128\/AAC.00110-19","article-title":"Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug-Resistant HIV-1 Infection","volume":"63","author":"Beccari","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_120","unstructured":"Kemnic, T.R., and Gulick, P.G. (2021, October 21). HIV Antiretroviral Therapy, Available online: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/30020680."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1517\/14656566.2010.509345","article-title":"Recent advances in antiretroviral drugs","volume":"12","author":"Ghosh","year":"2011","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"604261","DOI":"10.1155\/2012\/604261","article-title":"Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process","volume":"2012","author":"Adamson","year":"2012","journal-title":"Mol. Biol. Int."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1056\/NEJM199803263381301","article-title":"Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection","volume":"338","author":"Palella","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1097\/00002030-199910010-00017","article-title":"Natural history of HIV infection in the era of combination antiretroviral therapy","volume":"13","author":"Moore","year":"1999","journal-title":"Aids"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1056\/NEJMoa1105243","article-title":"Prevention of HIV-1 Infection with Early Antiretroviral Therapy","volume":"365","author":"Cohen","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1056\/NEJMoa1600693","article-title":"Antiretroviral Therapy for the Prevention of HIV-1 Transmission","volume":"375","author":"Cohen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Thomas, R., Galanakis, C., V\u00e9zina, S., Longpr\u00e9, D., Boissonnault, M., Huchet, E., Charest, L., Murphy, D., Trottier, B., and Machouf, N. (2015). Adherence to Post-Exposure Prophylaxis (PEP) and Incidence of HIV Seroconversion in a Major North American Cohort. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142534"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1586\/eri.11.20","article-title":"Post-exposure prophylaxis for HIV infection","volume":"9","author":"Rey","year":"2011","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1073\/pnas.90.1.25","article-title":"Quantitation of zidovudine-resistant human immunodeficiency virus type 1 in the blood of treated and untreated patients","volume":"90","author":"Mohri","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/BF02458429","article-title":"Understanding drug resistance for monotherapy treatment of HIV infection","volume":"59","author":"Kirschner","year":"1997","journal-title":"Bull. Math. Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4081\/idr.2013.s1.e5","article-title":"HIV drug resistance: Problems and perspectives","volume":"5","author":"Pennings","year":"2013","journal-title":"Infect. Dis. Rep."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev.pa.33.040193.001053","article-title":"HIV drug resistance","volume":"33","author":"Richman","year":"1993","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2165\/00003495-200969010-00003","article-title":"Novel targets for antiretroviral therapy: Clinical progress to date","volume":"69","author":"Dau","year":"2009","journal-title":"Drugs"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Cunha, R.F., Sim\u00f5es, S., Carvalheiro, M., Pereira, J.M.A., Costa, Q., and Ascenso, A. (2021). Novel Antiretroviral Therapeutic Strategies for HIV. Molecules, 26.","DOI":"10.3390\/molecules26175305"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1097\/QAD.0000000000002883","article-title":"Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: A multivariable analysis","volume":"35","author":"Cutrell","year":"2021","journal-title":"AIDS"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/QAI.0000000000002466","article-title":"Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials","volume":"85","author":"Rizzardini","year":"2020","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"9191","DOI":"10.1039\/C8OB02753F","article-title":"Identification of thienopyridine carboxamides as selective binders of HIV-1 trans Activation Response (TAR) and Rev Response Element (RRE) RNAs","volume":"16","author":"Li","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"16470","DOI":"10.1074\/jbc.RA120.015444","article-title":"Co-crystal structures of HIV TAR RNA bound to lab-evolved proteins show key roles for arginine relevant to the design of cyclic peptide TAR inhibitors","volume":"295","author":"Chavali","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1039\/D1SC00933H","article-title":"Targeting structural features of viral genomes with a nano-sized supramolecular drug","volume":"12","author":"Melidis","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Sosic, A., Olivato, G., Carraro, C., G\u00f6ttlich, R., Fabris, D., and Gatto, B. (2021). Bis-3-Chloropiperidines Targeting TAR RNA as A Novel Strategy to Impair the HIV-1 Nucleocapsid Protein. Molecules, 26.","DOI":"10.3390\/molecules26071874"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9611","DOI":"10.1021\/acs.jmedchem.8b01076","article-title":"Discovery of a Branched Peptide That Recognizes the Rev Response Element (RRE) RNA and Blocks HIV-1 Replication","volume":"61","author":"Dai","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"7190","DOI":"10.1038\/s41598-020-64120-2","article-title":"Nucleic acid recognition and antiviral activity of 1,4-substituted terphenyl compounds mimicking all faces of the HIV-1 Rev protein positively-charged \u03b1-helix","volume":"10","author":"Sedgwick","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/cmdc.200700194","article-title":"Inhibition of HIV-1 by a Peptide Ligand of the Genomic RNA Packaging Signal \u03a8","volume":"3","author":"Dietz","year":"2008","journal-title":"ChemMedChem"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"5462","DOI":"10.1021\/jm900599v","article-title":"Identification of specific small molecule ligands for stem loop 3 ribonucleic acid of the packaging signal \u03a8 of human immunodeficiency virus-1","volume":"52","author":"Warui","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12977-018-0407-4","article-title":"An RNA-binding compound that stabilizes the HIV-1 gRNA packaging signal structure and specifically blocks HIV-1 RNA encapsidation","volume":"15","author":"Ingemarsdotter","year":"2018","journal-title":"Retrovirology"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12977-018-0408-3","article-title":"Pre-exposure prophylaxis (PrEP) in an era of stalled HIV prevention: Can it change the game?","volume":"15","author":"Eakle","year":"2018","journal-title":"Retrovirology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e831","DOI":"10.1016\/S2352-3018(19)30196-1","article-title":"Global, regional, and national incidence, prevalence, and mortality of HIV, 1980\u20132017, and forecasts to 2030, for 195 countries and territories: A systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017","volume":"6","author":"Frank","year":"2019","journal-title":"Lancet HIV"},{"key":"ref_148","unstructured":"(2021, October 21). Assessing Global HIV Targets in PEPFAR Countries: A Dashboard. Available online: https:\/\/www.kff.org\/global-health-policy\/issue-brief\/assessing-global-hiv-targets-in-pepfar-countries-a-dashboard\/#."},{"key":"ref_149","unstructured":"(2014). UNAIDS Joint United Nations; Programme on HIV\/AIDS 90-90-90 An ambitious treatment target to help end the AIDS epidemic. United Nations, 40."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"83","DOI":"10.24875\/AIDSRev.M18000020","article-title":"Is UNAIDS 90-90-90 Target a Dream or a Reality for Middle East and North Africa Region on Ending the AIDS Epidemic? A Review Study","volume":"20","author":"Joulaei","year":"2019","journal-title":"Aids Rev."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/QAI.0000000000001761","article-title":"Substantial Heterogeneity in Progress Toward Reaching the 90-90-90 HIV Target in the WHO European Region","volume":"79","author":"Porter","year":"2018","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/MLR.0000000000000308","article-title":"The lifetime medical cost savings from preventing HIV in the United States","volume":"53","author":"Schackman","year":"2015","journal-title":"Med. Care"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1001\/jamainternmed.2019.7108","article-title":"HIV Antiretroviral Therapy Costs in the United States, 2012\u20132018","volume":"180","author":"McCann","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"15109","DOI":"10.1073\/pnas.96.26.15109","article-title":"HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression","volume":"96","author":"Davey","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e588","DOI":"10.1016\/S2352-3018(18)30173-5","article-title":"HIV drug resistance in low-income and middle-income countries","volume":"5","author":"Hamers","year":"2018","journal-title":"Lancet HIV"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.coph.2019.03.003","article-title":"Phylogenies in ART: HIV reservoirs, HIV latency and drug resistance","volume":"48","author":"Bandera","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1097\/QAD.0000000000002887","article-title":"Global estimates for the lifetime cost of managing HIV","volume":"35","author":"Tran","year":"2021","journal-title":"AIDS"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/cpt.1208","article-title":"HIV\/AIDS Vaccines: 2018","volume":"104","author":"Robinson","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.chom.2020.03.014","article-title":"The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies","volume":"27","author":"Cohn","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.02.005","article-title":"The rational design of an AIDS vaccine","volume":"124","author":"Douek","year":"2006","journal-title":"Cell"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"13","DOI":"10.29328\/journal.aaai.1001013","article-title":"HIV-1 Immune evasion: The main obstacle toward a successful vaccine","volume":"2","author":"Amitis","year":"2018","journal-title":"Arch. Asthma, Allergy Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nm.4119","article-title":"HIV-1 immune evasion\u2014A threat to effective vaccines?","volume":"22","author":"Rolland","year":"2016","journal-title":"Nat. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1089\/aid.2012.0171","article-title":"Targeting of Conserved Gag-Epitopes in Early HIV Infection Is Associated with Lower Plasma Viral Load and Slower CD4 + T Cell Depletion","volume":"29","author":"Perez","year":"2013","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nm1520","article-title":"CD8+ T-cell responses to different HIV proteins have discordant associations with viral load","volume":"13","author":"Kiepiela","year":"2007","journal-title":"Nat. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"954806","DOI":"10.1155\/2013\/954806","article-title":"Innate Immune Evasion Strategies by Human Immunodeficiency Virus Type 1","volume":"2013","author":"Guha","year":"2013","journal-title":"ISRN AIDS"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1146\/annurev.med.53.082901.104024","article-title":"The Challenge of Viral Reservoirs in HIV-1 Infection","volume":"53","author":"Blankson","year":"2002","journal-title":"Annu. Rev. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1097\/COH.0b013e32832f00c0","article-title":"HIV-1-specific antibody responses during acute and chronic HIV-1 infection","volume":"4","author":"Tomaras","year":"2009","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Overbaugh, J., and Morris, L. (2012). The Antibody Response against HIV-1. Cold Spring Harb. Perspect. Med., 2.","DOI":"10.1101\/cshperspect.a007039"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/31514","article-title":"The antigenic structure of the HIV gp120 envelope glycoprotein","volume":"393","author":"Wyatt","year":"1998","journal-title":"Nature"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/imr.12507","article-title":"The HIV-1 envelope glycoprotein structure: Nailing down a moving target","volume":"275","author":"Ward","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3389\/fmicb.2017.00390","article-title":"Driving HIV-1 into a Vulnerable corner by taking advantage of viral adaptation and evolution","volume":"8","author":"Harada","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/QAD.0000000000000106","article-title":"Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection","volume":"28","author":"Hraber","year":"2014","journal-title":"AIDS"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1111\/febs.13530","article-title":"The HIV glycan shield as a target for broadly neutralizing antibodies","volume":"282","author":"Doores","year":"2015","journal-title":"FEBS J."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/s41590-018-0235-7","article-title":"Recent progress in broadly neutralizing antibodies to HIV","volume":"19","author":"Sok","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"13232","DOI":"10.1128\/JVI.78.23.13232-13252.2004","article-title":"Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies","volume":"78","author":"Binley","year":"2004","journal-title":"J. Virol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"6187","DOI":"10.1128\/JVI.00239-07","article-title":"Neutralizing Antibody Responses in Acute Human Immunodeficiency Virus Type 1 Subtype C Infection","volume":"81","author":"Gray","year":"2007","journal-title":"J. Virol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"7538","DOI":"10.1128\/jvi.66.12.7538-7542.1992","article-title":"Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody","volume":"66","author":"Gorny","year":"1992","journal-title":"J. Virol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1126\/science.1178746","article-title":"Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target","volume":"326","author":"Walker","year":"2009","journal-title":"Science"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"103118","DOI":"10.1016\/j.ebiom.2020.103118","article-title":"Viral reservoirs in elite controllers of HIV-1 infection: Implications for HIV cure strategies","volume":"62","author":"Woldemeskel","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.immuni.2007.08.010","article-title":"Human Immunodeficiency Virus Controllers: Mechanisms of Durable Virus Control in the Absence of Antiretroviral Therapy","volume":"27","author":"Deeks","year":"2007","journal-title":"Immunity"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nri3478","article-title":"Unravelling the mechanisms of durable control of HIV-1","volume":"13","author":"Walker","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1517\/14712590802571928","article-title":"Elite control of HIV infection: Implications for vaccine design","volume":"9","author":"Baker","year":"2009","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41586-020-2651-8","article-title":"Distinct viral reservoirs in individuals with spontaneous control of HIV-1","volume":"585","author":"Jiang","year":"2020","journal-title":"Nature"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nature07352","article-title":"Challenges in the development of an HIV-1 vaccine","volume":"455","author":"Barouch","year":"2008","journal-title":"Nature"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/14712598.2017.1282457","article-title":"Current views on the potential for development of a HIV vaccine","volume":"17","author":"Cohen","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nri1307","article-title":"Identifying epitopes of HIV-1 that induce protective antibodies","volume":"4","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1146\/annurev.immunol.24.021605.090557","article-title":"GP120: Target for Neutralizing HIV-1 Antibodies","volume":"24","author":"Pantophlet","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-immunol-030409-101256","article-title":"The Role of Antibodies in HIV Vaccines","volume":"28","author":"Mascola","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev-immunol-041015-055515","article-title":"Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design","volume":"34","author":"Burton","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1126\/science.1061692","article-title":"Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design","volume":"293","author":"Saphire","year":"2001","journal-title":"Science"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0140-6736(18)31311-4","article-title":"HIV","volume":"392","author":"Ghosn","year":"2018","journal-title":"Lancet"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/326249a0","article-title":"Immunization against AIDS in humans","volume":"326","author":"Zagury","year":"1987","journal-title":"Nature"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nrmicro2911","article-title":"Animal models for HIV\/AIDS research","volume":"10","author":"Hatziioannou","year":"2015","journal-title":"Nat Rev Microbiol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fimmu.2016.00012","article-title":"Animal Models for HIV Cure Research","volume":"7","author":"Policicchio","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/laban.1279","article-title":"Tackling HIV and AIDS: Contributions by non-human primate models","volume":"46","year":"2017","journal-title":"Lab Anim."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"590780","DOI":"10.3389\/fimmu.2020.590780","article-title":"Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions","volume":"11","author":"Chasara","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"3502","DOI":"10.1016\/j.vaccine.2013.05.018","article-title":"A brief history of the global effort to develop a preventive HIV vaccine","volume":"31","author":"Esparza","year":"2013","journal-title":"Vaccine"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa0908492","article-title":"Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand","volume":"361","author":"Pitisuttithum","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Pitisuttithum, P., Rerks-Ngarm, S., Bussaratid, V., Dhitavat, J., Maekanantawat, W., Pungpak, S., Suntharasamai, P., Vanijanonta, S., Nitayapan, S., and Kaewkungwal, J. (2011). Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B\/E Vaccination in an Efficacy Trial in Thailand. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027837"},{"key":"ref_200","doi-asserted-by":"crossref","unstructured":"Zolla-Pazner, S., DeCamp, A., Gilbert, P.B., Williams, C., Yates, N.L., Williams, W.T., Howington, R., Fong, Y., Morris, D.E., and Soderberg, K.A. (2014). Vaccine-Induced IgG Antibodies to V1V2 Regions of Multiple HIV-1 Subtypes Correlate with Decreased Risk of HIV-1 Infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087572"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1089\/aid.2012.0103","article-title":"The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120","volume":"28","author":"Karasavvas","year":"2012","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nbt.3187","article-title":"COMPASS identifies T-cell subsets correlated with clinical outcomes","volume":"33","author":"Lin","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1056\/NEJMoa1113425","article-title":"Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial","volume":"366","author":"Haynes","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1093\/infdis\/jix099","article-title":"Randomized, Double-Blind Evaluation of Late Boost Strategies for HIV-Uninfected Vaccine Recipients in the RV144 HIV Vaccine Efficacy Trial","volume":"215","author":"Pitisuttithum","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1016\/S2352-3018(19)30406-0","article-title":"Late boosting of the RV144 regimen with AIDSVAX B\/E and ALVAC-HIV in HIV-uninfected Thai volunteers: A double-blind, randomised controlled trial","volume":"7","author":"Pitisuttithum","year":"2020","journal-title":"Lancet HIV"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1056\/NEJMoa2031499","article-title":"Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120\u2013MF59 in Adults","volume":"384","author":"Gray","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1128\/JVI.02108-09","article-title":"Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies","volume":"84","author":"Seaman","year":"2010","journal-title":"J. Virol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nm1461","article-title":"Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants","volume":"13","author":"Fischer","year":"2007","journal-title":"Nat. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/nm0310-268","article-title":"HIV vaccines: Mosaic approach to virus diversity","volume":"16","author":"Corey","year":"2010","journal-title":"Nat. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nm.2089","article-title":"Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys","volume":"16","author":"Barouch","year":"2010","journal-title":"Nat. Med."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nm.2108","article-title":"Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys","volume":"16","author":"Santra","year":"2010","journal-title":"Nat. Med."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S0140-6736(18)31364-3","article-title":"Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1\/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19)","volume":"392","author":"Barouch","year":"2018","journal-title":"Lancet"},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Sanders, R.W., Derking, R., Cupo, A., Julien, J.-P., Yasmeen, A., de Val, N., Kim, H.J., Blattner, C., de la Pe\u00f1a, A.T., and Korzun, J. (2013). A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003618"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Sanders, R.W., Van Gils, M.J., Derking, R., Sok, D., Ketas, T.J., Burger, J.A., Ozorowski, G., Cupo, A., Simonich, C., and Goo, L. (2015). HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science, 349.","DOI":"10.1126\/science.aac4223"},{"key":"ref_215","unstructured":"(2021, October 21). A Study to Assess the Efficacy of a Heterologous Prime\/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV)-1 Infection in Women in Sub-Saharan Africa [NCT03060629], Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03060629."},{"key":"ref_216","unstructured":"(2021, October 21). Johnson & Johnson and Global Partners Announce Results from Phase 2b Imbokodo HIV Vaccine Clinical Trial in Young Women in Sub-Saharan Africa. Available online: https:\/\/www.janssen.com\/johnson-johnson-and-global-partners-announce-results-phase-2b-imbokodo-hiv-vaccine-clinical-trial."},{"key":"ref_217","unstructured":"(2021, October 29). A Study of Heterologous Vaccine Regimen of Adenovirus Serotype 26 Mosaic4 Human Immunodeficiency Virus(Ad26.Mos4.HIV), Adjuvanted Clade C gp140 and Mosaic gp140 to Prevent HIV-1 Infection Among Cis-gender Men and Transgender Individuals Who Have Sex With, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03964415."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/2\/138\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:19:02Z","timestamp":1760134742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/2\/138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,14]]},"references-count":217,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["toxins14020138"],"URL":"https:\/\/doi.org\/10.3390\/toxins14020138","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,14]]}}}