The complexity of genome integration process in human lentivirus
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Garcia-Vallejo, F. (2016). The complexity of genome integration process in human lentivirus. Revista De La Academia Colombiana De Ciencias Exactas, Físicas Y Naturales, 40(156), 382–394. https://doi.org/10.18257/raccefyn.364

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Abstract

Introduction: The distribution of human lentiviral cDNA into the host genome has been studied using a linear structural approach, however such analysis is incomplete because do not consider the dynamics and topology of interphase chromatin and the gene expression networks in infected cells.

Objective: To correlate using a non-linear approach the multifractality of human chromosomes, with the composition and disturbing of chromatin topology, as complex effect promote by the lentiviral cDNA integration.

Methods: From 2,409 human genome sequences flanking the 5’LTR of human and simian lentiviruses obtained from GeneBank (NCBI) database, several human genomic variables were correlated with the multifractality values AvΔDq of chromosomes covering more than 98.6% of the human genome. Moreover Cytoscape v.2.63 was used to simulate the effects of viral cDNA integration on gene expression networks in macrophages.

Results: 54.21% of lentivirus cDNA integrations were registered in chromosomes with high and medium fractality; 18.14% of these cDNA integrations was exclusively located in chromosomes 16, 17, 19 and 22 corresponding to that with high multifractality values. High scores of Pearson’s correlation for AvΔDq/chromosome vs integrations/chromosome; percentage of Alu sequences were recorded. 2,770 interactions among 28 genes located closed to HIV-1 proviruses in human macrophages were recorded. cDNA integration alters the gene interaction networks in infected cells, the topological parameters of non-infected macrophage network gene was dramatically changed upon HIV-1 integration.

Conclusion:Some topological changes in those regions with high frequency of cDNA viral integrations would synergistically configure local topological chromatin environments that alters the gene interaction networks in infected cells. © 2016. Acad. Colomb. Cienc. Ex. Fis. Nat. All rights reserved.

https://doi.org/10.18257/raccefyn.364
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References

Albanese A, Arosio D, Terreni M, Cereseto A. 2008. HIV-1 Pre-Integration Complexes Selectively Target Decondensed Chromatin in the Nuclear Periphery. PLoS one. 3: e2413. doi:10.1371/journal.pone.0002413.

Alzate LA, Domínguez MC, Sánchez A, Vélez P, Moreno PA, García-Vallejo F. 2015. Eventos fractales relacionados con fenómenos epigenéticos del genoma humano en la integración de los lentivirus humanos. Biomedica. 35: 53.

Balakrishnan S. 2009. Alternative paths in HIV-1 targeted human signal transduction pathways. BMC Genomics. 10 (Suppl 3):S30.

Bancaud A, Huet S, Daigle N, Mozziconacci J, Beaudouin J, Ellenberg J. 2009. Molecular crowding affects diffusion and binding of nuclear proteins in heterochromatin and reveals the fractal organization of chromatin. EMBO J. 28 (24):3785-98.

Bancaud A, Lavelle C, Huet S, Ellenberg J. 2012. A fractal model for nuclear organization: current evidence and biological implications. Nucleic Acids Res. 40 (18):8783-92.

Barr S, Ciuffi A, Leipzig J, Shinn P, Ecker J, Bushman F. 2006. HIV Integration site selection: targeting in macrophages and the effects of different routes of viral entry. Mol. Ther. 14:218-25.

Benleulmi MS, Matysiak J, Henriquez DR, Vaillant C, Lesbats P, Calmels C, Naughtin M, et al. 2015. Intasome architecture and chromatin density modulate retroviral integration into nucleosome. Retrovirology.12:13.

Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, Müller S. 2005. Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol. 3 (5):e157.

Carteau S, Hoffmann C, Bushman F. 1998. Chromosome structure and human immunodeficiency virus type 1 cDNA integration: centromeric alphoid repeats are a disfavored target. J. Virol. 72: 4005-4014.

Cattoglio C, Pellin D, Rizzi E, Maruggi G, Corti G, Miselli F, Sartori D, et al. 2010. High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors. Blood.116 (25):5507-17.

Cereseto A, and Giacca M. 2004. Integration site selection by retroviruses. AIDS Rev 6:13-21.

Chakraborty S, Mehta I, Kulashreshtha M, Rao BJ. 2015. Quantitative analysis of chromosome localization in the nucleus. Methods Mol Biol. 1228: 223-33.

Ciuffi A, Llano M, Poeschla E, Hoffmann C, Leipzig J, Shinn P, Ecker JR, et l. 2005. A role for LEDGF/p75 in targeting HIV DNA integration. Nat. Med. 11:1287-89.

Ciuffi A. 2008. Mechanisms governing lentivirus integration site selection. Curr GeneTher.; 8: 419-29.

Coffer PJ, Jin J, Woodgett JR, 1998. Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J. 335 (1):1-13.

Coffin JM. Retroviridae and their replication In Virology, 1996. ed. BN Fields et al., Raven Press, New York. pp. 1767–1848.

Colin L, Verdin E, Van Lint C. 2014. HIV-1 Chromatin, Transcription, and the Regulatory Protein Tat. Methods. Mol Biol. 1087:85-101.

Craigie R, Bushman FD. 2014. Host Factors in Retroviral Integration and the Selection of Integration Target Sites. Microbiol Spectr. 2(6). doi: 10.1128.

Cremer M, Grasser F, Lanctot C, Muller S, Neusser M, Zinner R, Solovei I, et al. 2008. Multicolor 3D fluorescence in situ hybridization for imaging interphase chromosomes. Methods Mol Biol. 463:205-3.

Crise B, Li Y, Yuan C, Morcock DR, Whitby D, Munroe DJ, Arthur LO, et al. 2005. Simian immunodeficiency virus integration preference is similar to that of human immunodeficiency virus type 1. J Virol. 79:12199-204.

Cui M, Huang Y, Zhao Y, Zheng J. 2008. Transcription factor FOXO3a mediates apoptosis in HIV-1-infected macrophages. J. Immunol. 15 (2):898-906.

DeCerbo J, Carmichael GG. 2005. SINEs point to abundant editing in the human genome. Genome Biology. 216:1-4.

Demeulemeester J, De Rijck J, Gijsbers R, Debyser Z. 2015 Retroviral integration: Site matters: Mechanisms and consequences of retroviral integration site selection. Bioessays. 37(11):1202-14.

Derse D, Crise B, Li Y, Princler G, Stewart C, Connor F, Hughes H, et al. 2007. HTLV-1 integration target sites in the human genome: comparison with other retroviruses. J. virol. 81: 6731-6741.

Diehl AG, Boyle AP. 2016. Deciphering ENCODE. Trends Genet. 32(4):238-49.

The ENCODE Project Consortium. 2012. Nature 489, 57–74.

ENCODE Project Consortium. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 447(7146):799-816.

Felice B, Cattoglio C, Cittaro D, Testa A, Miccio A, Ferrari G, Luzi L, et al. 2009. Transcription factor binding sites are genetic determinants of retroviral integration in the human genome. PLoS One. 4(2):e4571.

Ferris AL, Wu X, Hughes CM, Stewart C, Smith SJ, Milne TA, Wang GG, et al. 2010. Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration. Proc. natl. acad. sci. USA. 107: 3135-40.

Folle GA. 2008. Nuclear architecture, chromosome domains and genetic damage. Mutat Res. 658(3):172-83.

García-Vallejo F, Domínguez MC, Sánchez A, Vélez P, Moreno P. 2015. Integración preferencial del ADN complementario de los lentivirus humanos en cromosomas con alto nivel de multifractalidad. Biomédica.35: 54.

Geyer PK, Vitalini MW, Wallrath LL. 2011 Nuclear organization: taking a position on gene expression. Curr Opin Cell Biol.23 (3):354-9.

Folle GA. 2008. Nuclear architecture, chromosome domains and genetic damage. Mutat Res. 658(3):172-83.

Hematti P, Hong BK, Ferguson C, Adler R, Hanawa H, Sellers S, Ingeborg E. 2004. Distinct Genomic Integration of MLV and SIV Vectors in Primate Hematopoietic Stem and Progenitor Cells. PLoS Biol. 2: E423.

Hindmarsh P, Leis J. 1999. Retroviral DNA integration. Microbiol mol. biol. rev. 63: 836-84.

Ideker T, Ozier O, Schwikowski B, Siegel AF. 2002. Discovering regulatory and signaling circuits in molecular interaction networks. Bioinformatics 18: S233–S240.

Ikeda T, Shibata J, Yoshimura K, Koito A, Matsushita S. 2007. Recurrent HIV-1 integration at the BACH2 locus in resting CD4+ T cell populations during effective highly active antiretroviral therapy. J Infect Dis.195 (5):716-25.

International human genome sequencing consortium. 2004. Finishing the euchromatic sequence of the human genome. Nature. 431: 931-45.

Jordan A, Defechereux P, Verdin E. 2001.The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation. The EMBO J. 20:1726-38.

Karimi-Busheri F, Rasouli-Nia A. 2015. Integration, Networking, and Global Biobanking in the Age of New Biology. Adv Exp Med Biol.864:1-9.

Kaur G, Sharma G, Kumar N, Kaul MH, Bansal RA, Vajpayee M, Wig N. et al. 2013. Genomic architecture of HIV-1 infection: current status & challenges. Indian J Med Res.138 (5):663-81.

Klug M, Heinz S, Gebhard C, Schwarzfischer L, Krause SW, Andreesen R, Rehli M. 2010. Active DNA demethylation in human postmitoticcells correlates with activating histone modifications, but not transcription levels. Genome Biol. 11 (16), R63.

Kowalczyk JE, Zablocka B. 2008. Protein kinases in mitochondria. Postepy Biochem. 54, 209-16.

Lanctôt C, Cheutin T, Cremer M, Cavalli G, Cremer T. 2007. Dynamicgenome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet. 8(2):104-15.

Le Sage V, Mouland AJ, Valiente-Echeverría F. 2014. Roles of HIV-1 capsid in viral replication and immune evasion. Virus Res.193:116-29.

Lee SR, Park JH, Park EK, Chung CH, Kang SS, Bang OS. 2005. Akt- nduced promotion of cell-cycle progression at G2/M phase involves upregulation of NF-Y binding activity in PC12 cells. J. Cell. Physiol. 205 (2), 270-77.

Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, et al. 2007. The diploid genome sequence of an individual human. PLoS Biol. 5:e254.

Lewinski M, Yamashita M, Emerman M, Ciuffi A, Marshall H, Crawford G. 2006. Retroviral DNA Integration: Viral and Cellular Determinants of Target-Site Selection. PLoS pathog. 2: 0611-0622.

Losa GA. 2009.The fractal geometry of life. Riv Biol.102 (1):29-59.

MacNeil A, Sankale JL, Meloni S, Sarr A, Mboup S, Kanki P. 2006. Genomic Sites of Human Immunodeficiency Virus Type 2 (HIV-2) Integration: Similarities to HIV-1 In Vitro and Possible Differences In Vivo. J. virol. 80: 7316-21.

Maere S, Heymans K, Kuiper M. 2005. BiNGO: a cytoscape plug-in to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21(16):3448-49.

Manjunath N, Yi G, Dang Y, Shankar P. 2013. Newer gene editing technologies toward HIV gene therapy. Viruses. 5(11):2748-66.

Bauman JD, Patel D, Arnold E. 2012. Fragment screening and HIV therapeutics. Top Curr Chem.317:181-200.

Margolis DA, Boffito M. 2015. Long-acting antiviral agents for HIV treatment. Curr Opin HIV AIDS.10 (4):246-52.

Maxfield L, Fraize C, Coffin JM. 2005. Relationship between retroviral DNA-integration site selection and host cell transcription. Proc natl. acad. Sci USA. 102: 1436-44.

Mcsweeney. Google Summer of Code 2008. http://sites.google.com/site/randomnetworkplugin/. Meaburn KJ, Misteli T. Cell biology: chromosome territories. Nature. 2007; 445(7126):379-81.

Méndez C, Ahlenstiel CL, Kelleher AD. 2015. Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus. World J Virol. 4(3):219-44.

Mitchell RS, Beitzel BF, Schroder AR, Shinn P, Chen H, Berry CC, Ecker JR et al. 2004. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol. 2(8):E234.

Moore J.P, Stevenson M. 2000.New Targets for Inhibitors of HIV-1 Replication. Nature Rev.1: 40-9.

Moraes F, Góes A. 2016. A decade of human genome project conclusion: Scientific diffusion about our genome knowledge. Biochem Mol Biol Educ. Mar 7. doi: 10.1002/bmb.20952.

Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, et al. 2001. Initial sequencing and analysis of the human genome. Nature. 409:860-921.

Moreno PA, Vélez PE, Martínez E, Garreta LE, Díaz N, Amador S, Tischer I, et al. 2011. The human genome: a multifractal analysis. BMC Genomics.12:506. doi: 10.1186/1471-2164-12-506.

Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis R, Tissenbaum HA, Piot P, UNAIDS–Lancet Commission. 2015. Defeating AIDS advancing global health. Lancet.386:171-218.

Polychronopoulos D, Athanasopoulou L, Almirantis Y. 2016 Fractality and entropic scaling in the chromosomal distribution of conserved noncoding elements in the human genome. Gene. Feb 17. pii: S0378-1119.

Provata A, Katsaloulis P. 2010. Hierarchical multifractal representation of symbolic sequences and application to human chromosomes. Phys Rev E Stat Nonlin Soft Matter Phys. 81:26-102.

Rick SM, Beitzel BF, Schroder AR, Shinn P, Chen H, Berry CC, Ecker JR, et al. 2004. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol .2: 1127-37.

Saayman S, Ali SA, Morris KV, Weinberg MS. 2015. The therapeutic application of CRISPR/Cas9 technologies for HIV. Expert Opin Biol Ther.15 (6):819-3.

Saeed AI, Bhagabati NK, Braisted JC, Liang W, Sharov W, Howe V, Li J, et al. 2006. TM4 microarray software suite. Methods Enzymol. 411:134- 93.

Schröder A, Shinn P, Chen H, Berry C, Ecker JR, Bushman F. 2002. HIV- Integration in the Human Genome Favors Active Genes and Local Hotspots. Cell.110:521-29.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N. 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13 (11), 2498–2504.

Sierra S, Kupfer B, Kaiser R. 2005. Basics of the virology of HIV-1 and its replication. J. Clin. Virol. 34: 233-44.

Simonis M, Klous P, Splinter E, Moshkin Y, Willemsen R, de Wit E, van Steensel B, et al. 2006. Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C) Nature Gen. 38:1348-54.

Song G, Ouyang G, Bao S. 2005. The activation of Akt/PKB signaling pathway and cell survival. J. Cell. Mol. Med. 9 (1):59-71.

Soto J, Peña A, Salcedo M, Domínguez MC, Sánchez A, García- allejo F. 2010. Caracterización Genómica de la Integración In vitro del VIH-1 en células mononucleares de sangre periférica, macrófagos, y células T de Jurkat. Infectio. 14: 20-30.

Soto J, Peña A, García-Vallejo F. 2011. A genomic and bioinformatics analysis of the integration of HIV in peripheral blood mononuclear cells. AIDS Res Hum Retroviruses. 27:547-55.

Soto-Girón MJ, García-Vallejo F. 2012. Changes in the topology of gene expression networks by human immunodeficiency virus type 1 (HIV-1) integration in macrophages. Virus Res. 163(1):91-7.

UNAIDS JUNPoHA Global Report: UNAIDS report on the global AIDS epidemic. 2013.

Van Maele B, Busschots K, Vandekerckhove L, Christ F, Debyser Z. 2006. Cellular co-factors of VIH-1 integration. Trends Biochem. Sci. 31: 98–105.

Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, et al. 2001. The sequence of the human genome. Science. 291:1304-51.

Versteeg R, van Schaik BDC, van Batenburg MF, Roos M, Monajemi R, Caron H, Bussemaker HJ, et al. 2003. The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Research 13:1998-2004.

Wang YJ, McKenna PM, Hrin R, Felock P, Lu M, Jones KG, Coburn CA, Grobler JA. 2010. Assessment of the susceptibility of mutant HIV-1 to antiviral agents. J. virol methods. 165: 230-7.

Wong RW, Mamede JI, Hope TJ. 2015. Impact of Nucleoporin-Mediated Chromatin Localization and Nuclear Architecture on HIV Integration Site Selection. J Virol. 89(19):9702-5.

Wu X, Li Y, Crise B, Burgess SM. 2003. Transcription start regions in the human genome are favored targets for MLV integration. Science. 300: 1749-51.

Yi J, Stypula-Cyrus Y, Blaha CS, Roy HK, Backman V. 2015. Fractal Characterization of Chromatin Decompaction in Live Cells. Biophys J. 109(11):2218-26.

Zaccarelli M, Tozzi V, Lorenzini P, Trotta MP, Forbici F, Visco-Comandini U, Gori C, et al. 2005. Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients. AIDS.19:1081-89.

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