Abstract
The introduction of combination antiretroviral therapy (cART) has switched HIV-1 infection from a lethal disease to a chronic one. Indeed, cART is a lifelong treatment since its interruption is always followed by a rapid rebound of viremia from both cellular and anatomical viral reservoirs where the integrated HIV-1 provirus remains transcriptionally silent or maintains low-levels of viral replication, thereby preventing HIV-1 eradication. As therapeutic approach, the “shock and kill” strategy has emerged with the main objective to reactivate HIV-1 transcription from latency by using latency reversing agents (LRAs) prior to kill the reactivated infected cells by improving host immune responses. In this context, the development of tools such as HIV-1 latently infected cell lines have drastically increased our knowledge about HIV-1 latency and how to counteract this highly heterogeneous phenomenon. In this chapter, we will describe several chronically HIV-1 infected T-lymphocytic cell lines as useful surrogate models to study reversible HIV-1 proviral latency in CD4+ T cells in vitro before approaching more complex and expensive models.
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References
Dutilleul A, Rodari A, Van Lint C (2020) Depicting HIV-1 transcriptional mechanisms: a summary of what we know. Viruses 12:1385
Abner E, Jordan A (2019) HIV ‘shock and kill’ therapy: in need of revision. Antivir Res 166:19–34
Moranguinho I, Valente ST (2020) Block-and-lock: new horizons for a cure for HIV-1. Viruses 12:1443
Vansant G, Bruggemans A, Janssens J, Debyser Z (2020) Block-and-lock strategies to cure HIV infection. Viruses 12:84
Folks T et al (1985) Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proc Natl Acad Sci U S A 82:4539–4543
Telwatte S et al (2019) Heterogeneity in HIV and cellular transcription profiles in cell line models of latent and productive infection: implications for HIV latency. Retrovirology 16:32
Folks TM et al (1986) Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med 164:280–290
Lightfoote MM et al (1986) Structural characterization of reverse transcriptase and endonuclease polypeptides of the acquired immunodeficiency syndrome retrovirus. J Virol 60:771–775
Deichmann M, Bentz M, Haas R (1997) Ultra-sensitive FISH is a useful tool for studying chronic HIV-1 infection. J Virol Methods 65:19–25
Jackson JB et al (1993) Establishment of a quality assurance program for human immunodeficiency virus type 1 DNA polymerase chain reaction assays by the AIDS Clinical Trials Group. ACTG PCR Working Group, and the ACTG PCR Virology Laboratories. J Clin Microbiol 31:3123–3128
Bourinbaiar AS, Ajuang-Simbiri K (1996) Simple procedure for estimating the efficiency of PCR. Mol Biotechnol 6:87–89
Busby E et al (2017) Instability of 8E5 calibration standard revealed by digital PCR risks inaccurate quantification of HIV DNA in clinical samples by qPCR. Sci Rep 7:1209
Wilburn KM et al (2016) Heterogeneous loss of HIV transcription and proviral DNA from 8E5/LAV lymphoblastic leukemia cells revealed by RNA FISH:FLOW analyses. Retrovirology 13:55
Clouse KA et al (1989) Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J Immunol 142:431–438
Folks TM et al (1989) Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci U S A 86:2365–2368
Gimble JM et al (1988) Activation of the human immunodeficiency virus long terminal repeat by herpes simplex virus type 1 is associated with induction of a nuclear factor that binds to the NF-kappa B/core enhancer sequence. J Virol 62:4104–4112
Poli G et al (1990) Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci U S A 87:782–785
Biswas P et al (1995) Cross-linking of CD30 induces HIV expression in chronically infected T cells. Immunity 2:587–596
Takahashi Y et al (2001) OX40 stimulation by gp34/OX40 ligand enhances productive human immunodeficiency virus type 1 infection. J Virol 75:6748–6757
Stanley SK, Bressler PB, Poli G, Fauci AS (1990) Heat shock induction of HIV production from chronically infected promonocytic and T cell lines. J Immunol 145:1120–1126
Shankaran P, Vlkova L, Liskova J, Melkova Z (2011) Heme arginate potentiates latent HIV-1 reactivation while inhibiting the acute infection. Antivir Res 92:434–446
Thierry S et al (2007) High-mobility group box 1 protein induces HIV-1 expression from persistently infected cells. AIDS 21:283–292
Scheller C et al (2004) CpG oligodeoxynucleotides activate HIV replication in latently infected human T cells. J Biol Chem 279:21897–21902
Papp B, Byrn RA (1995) Stimulation of HIV expression by intracellular calcium pump inhibition. J Biol Chem 270:10278–10283
Savarino A et al (2009) ‘Shock and kill’ effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence. Retrovirology 6:52
Gunst JD et al (2019) Fimepinostat, a novel dual inhibitor of HDAC and PI3K, effectively reverses HIV-1 latency ex vivo without T cell activation. J Virus Erad 5:133–137
Laughlin MA, Chang GY, Oakes JW, Gonzalez-Scarano F, Pomerantz RJ (1995) Sodium butyrate stimulation of HIV-1 gene expression: a novel mechanism of induction independent of NF-kappa B. J Acquir Immune Defic Syndr Hum Retrovirol 9:332–339
Palmisano I et al (2012) Amino acid starvation induces reactivation of silenced transgenes and latent HIV-1 provirus via down-regulation of histone deacetylase 4 (HDAC4). Proc Natl Acad Sci U S A 109:E2284–E2293
Perez VL et al (1991) An HIV-1-infected T cell clone defective in IL-2 production and Ca2+ mobilization after CD3 stimulation. J. Immunol 147:3145–3148
Symons J et al (2017) HIV integration sites in latently infected cell lines: evidence of ongoing replication. Retrovirology 14:2
Iwase SC et al (2019) HIV-1 DNA-capture-seq is a useful tool for the comprehensive characterization of HIV-1 provirus. Sci Rep 9:12326
Okutomi T, Minakawa S, Hirota R, Katagiri K, Morikawa Y (2020) HIV reactivation in latently infected cells with Virological synapse-like cell contact. Viruses 12:417
Jordan A, Bisgrove D, Verdin E (2003) HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. EMBO J 22:1868–1877
Emiliani S et al (1996) A point mutation in the HIV-1 tat responsive element is associated with postintegration latency. Proc Natl Acad Sci U S A 93:6377–6381
Emiliani S et al (1998) Mutations in the tat gene are responsible for human immunodeficiency virus type 1 postintegration latency in the U1 cell line. J Virol 72:1666–1670
Antoni BA, Rabson AB, Kinter A, Bodkin M, Poli G (1994) NF-kappa B-dependent and -independent pathways of HIV activation in a chronically infected T cell line. Virology 202:684–694
Gaynor R (1992) Cellular transcription factors involved in the regulation of HIV-1 gene expression. AIDS 6:347–363
Bachu M et al (2012) Multiple NF-κB sites in HIV-1 subtype C long terminal repeat confer superior magnitude of transcription and thereby the enhanced viral predominance. J Biol Chem 287:44714–44735
Pearson R et al (2008) Epigenetic silencing of human immunodeficiency virus (HIV) transcription by formation of restrictive chromatin structures at the viral long terminal repeat drives the progressive entry of HIV into latency. J Virol 82:12291–12303
Bosch V, Pawlita M (1990) Mutational analysis of the human immunodeficiency virus type 1 env gene product proteolytic cleavage site. J Virol 64:2337–2344
Han Y et al (2004) Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes. J Virol 78:6122–6133
Spivak AM, Planelles V (2018) Novel latency reversal agents for HIV-1 cure. Annu Rev Med 69:421–436
Yukl SA et al (2018) HIV latency in isolated patient CD4+ T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing. Sci Transl Med 10:eaap9927
Vermeire J et al (2012) Quantification of reverse transcriptase activity by real-time PCR as a fast and accurate method for titration of HIV, Lenti- and Retroviral vectors. PLoS One 7:e50859
Acknowledgments
CVL acknowledges funding from the Belgian National Fund for Scientific Research (FRS-FNRS, Belgium), the European Union′s Horizon 2020 research and innovation programme (grant agreement No 691119-EU4HIVCURE-H2020-MSCA-RISE-2015), the “Fondation Roi Baudouin”, the NEAT (European AIDSTreatment Network) program, the “Fondation Roi Baudouin”, the Internationale Brachet Stiftung (IBS), ViiVHealthcare, the Walloon Region (Fonds de Maturation), “Les Amis des Instituts Pasteur á Bruxelles, asbl.”, andthe University of Brussels (ULB - Action de Recherche Concertée (ARC) grant) related to her work on HIVlatency. The laboratory of CVL is part of the ULB-Cancer Research Centre (U-CRC). AR is a postdoctoral fellow(ULB ARC program). CVL is “Directeur de Recherches” of the F.R.S-FNRS.
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Rodari, A., Poli, G., Van Lint, C. (2022). Jurkat-Derived (J-Lat, J1.1, and Jurkat E4) and CEM-Derived T Cell Lines (8E5 and ACH-2) as Models of Reversible Proviral Latency. In: Poli, G., Vicenzi, E., Romerio, F. (eds) HIV Reservoirs. Methods in Molecular Biology, vol 2407. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1871-4_1
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DOI: https://doi.org/10.1007/978-1-0716-1871-4_1
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