[en] Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of the infected cells (mitotic cycle). The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone). We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1) initial integration inside genes or promoters and (2) host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in transcribed regions.
Disciplines :
Immunology & infectious disease
Author, co-author :
Gillet, Nicolas ; Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Gutiérrez, Gerónimo
Rodriguez, Sabrina ; Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
De Brogniez, Alix ; Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Renotte, Nathalie ; Université de Liège - ULiège > GIGA-R : Epigénétique Cellulaire et Moléculaire
Alvarez, Irene
Trono, Karina
Willems, Luc ; Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Language :
English
Title :
Massive Depletion of Bovine Leukemia Virus Proviral Clones Located in Genomic Transcriptionally Active Sites During Primary Infection
Publication date :
2013
Journal title :
PLoS Pathogens
ISSN :
1553-7366
eISSN :
1553-7374
Publisher :
Public Library of Science, San Francisco, United States - California
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Bibliography
Peeters M, Delaporte E, (2012) Simian retroviruses in African apes. Clin Microbiol Infect 18: 514-520.
Cook LB, Elemans M, Rowan AG, Asquith B, (2013) HTLV-1: persistence and pathogenesis. Virology 435: 131-140.
Gillet N, Florins A, Boxus M, Burteau C, Nigro A, et al. (2007) Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human. Retrovirology 4: 18.
Matsuoka M, Jeang KT, (2011) Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ and therapy. Oncogene 30: 1379-1389.
Pais-Correia AM, Sachse M, Guadagnini S, Robbiati V, Lasserre R, et al. (2010) Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat Med 16: 83-89.
Nejmeddine M, Bangham CR, (2010) The HTLV-1 Virological Synapse. Viruses 2: 1427-1447.
Jones KS, Lambert S, Bouttier M, Benit L, Ruscetti FW, et al. (2011) Molecular aspects of HTLV-1 entry: functional domains of the HTLV-1 surface subunit (SU) and their relationships to the entry receptors. Viruses 3: 794-810.
Lairmore MD, Anupam R, Bowden N, Haines R, Haynes RA 2nd, et al. (2011) Molecular determinants of human T-lymphotropic virus type 1 transmission and spread. Viruses 3: 1131-1165.
Edwards D, Fenizia C, Gold H, de Castro-Amarante MF, Buchmann C, et al. (2011) Orf-I and orf-II-encoded proteins in HTLV-1 infection and persistence. Viruses 3: 861-885.
Mortreux F, Kazanji M, Gabet AS, de Thoisy B, Wattel E, (2001) Two-step nature of human T-cell leukemia virus type 1 replication in experimentally infected squirrel monkeys (Saimiri sciureus). J Virol 75: 1083-1089.
Pomier C, Alcaraz MT, Debacq C, Lancon A, Kerkhofs P, et al. (2008) Early and transient reverse transcription during primary deltaretroviral infection of sheep. Retrovirology 5: 16.
Cavrois M, Wain-Hobson S, Gessain A, Plumelle Y, Wattel E, (1996) Adult T-cell leukemia/lymphoma on a background of clonally expanding human T-cell leukemia virus type-1-positive cells. Blood 88: 4646-4650.
Etoh K, Tamiya S, Yamaguchi K, Okayama A, Tsubouchi H, et al. (1997) Persistent clonal proliferation of human T-lymphotropic virus type I-infected cells in vivo. Cancer Res 57: 4862-4867.
Cavrois M, Leclercq I, Gout O, Gessain A, Wain-Hobson S, et al. (1998) Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with Tropical spastic paraparesis/HTLV-1 associated myelopathy. Oncogene 17: 77-82.
Gabet AS, Gessain A, Wattel E, (2003) High simian T-cell leukemia virus type 1 proviral loads combined with genetic stability as a result of cell-associated provirus replication in naturally infected, asymptomatic monkeys. Int J Cancer 107: 74-83.
Gillet NA, Malani N, Melamed A, Gormley N, Carter R, et al. (2011) The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones. Blood 117: 3113-3122.
Moules V, Pomier C, Sibon D, Gabet AS, Reichert M, et al. (2005) Fate of premalignant clones during the asymptomatic phase preceding lymphoid malignancy. Cancer Res 65: 1234-1243.
Melamed A, Laydon D, Gillet N, Tanaka Y, Taylor G, et al. (2013) Genome-wide determinants of proviral targeting, clonal abundance and expression in natural HTLV-1 Infection. PloS Pathogens 9: e1003271 doi:10.1371/journal.ppat.1003271.
Iwanaga M, Watanabe T, Utsunomiya A, Okayama A, Uchimaru K, et al. (2010) Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. Blood 116: 1211-1219.
Gutierrez G, Carignano H, Alvarez I, Martinez C, Porta N, et al. (2012) Bovine leukemia virus p24 antibodies reflect blood proviral load. BMC Vet Res 8: 187.
Gutierrez G, Alvarez I, Politzki R, Lomonaco M, Dus Santos MJ, et al. (2011) Natural progression of Bovine Leukemia Virus infection in Argentinean dairy cattle. Vet Microbiol 151: 255-263.
Gillet N, Cook L, Laydon D, Hlela C, Verdonck K, et al. (2013) Strongyloidiasis and Infective Dermatitis Alter Human T Lymphotropic Virus-1 Clonality in vivo. PLoS Pathogens 9: e1003263 doi:10.1371/journal.ppat.1003263.
Larsen F, Gundersen G, Lopez R, Prydz H, (1992) CpG islands as gene markers in the human genome. Genomics 13: 1095-1107.
Moqtaderi Z, Wang J, Raha D, White RJ, Snyder M, et al. (2010) Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells. Nat Struct Mol Biol 17: 635-640.
Meekings KN, Leipzig J, Bushman FD, Taylor GP, Bangham CR, (2008) HTLV-1 integration into transcriptionally active genomic regions is associated with proviral expression and with HAM/TSP. PLoS Pathog 4: e1000027.
Wu X, Li Y, Crise B, Burgess SM, Munroe DJ, (2005) Weak palindromic consensus sequences are a common feature found at the integration target sites of many retroviruses. J Virol 79: 5211-5214.
Holman AG, Coffin JM, (2005) Symmetrical base preferences surrounding HIV-1, avian sarcoma/leukosis virus, and murine leukemia virus integration sites. Proc Natl Acad Sci U S A 102: 6103-6107.
Wu X, Li Y, Crise B, Burgess SM, (2003) Transcription start regions in the human genome are favored targets for MLV integration. Science 300: 1749-1751.
Mitchell RS, Beitzel BF, Schroder AR, Shinn P, Chen H, et al. (2004) Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol 2: E234.
Wang GP, Ciuffi A, Leipzig J, Berry CC, Bushman FD, (2007) HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications. Genome Res 17: 1186-1194.
Lewinski MK, Yamashita M, Emerman M, Ciuffi A, Marshall H, et al. (2006) Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog 2: e60.
Derse D, Crise B, Li Y, Princler G, Lum N, et al. (2007) Human T-cell leukemia virus type 1 integration target sites in the human genome: comparison with those of other retroviruses. J Virol 81: 6731-6741.
Ciuffi A, Llano M, Poeschla E, Hoffmann C, Leipzig J, et al. (2005) A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med 11: 1287-1289.
Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, et al. (2013) Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study. PLoS Pathog 9: e1003211.
Bangham CR, (2009) CTL quality and the control of human retroviral infections. Eur J Immunol 39: 1700-1712.
Florins A, Gillet N, Asquith B, Boxus M, Burteau C, et al. (2007) Cell dynamics and immune response to BLV infection: a unifying model. Front Biosci 12: 1520-1531.
Florins A, de Brogniez A, Elemans M, Bouzar AB, Francois C, et al. (2012) Viral expression directs the fate of B cells in bovine leukemia virus-infected sheep. J Virol 86: 621-624.
Merezak C, Reichert M, Van Lint C, Kerkhofs P, Portetelle D, et al. (2002) Inhibition of histone deacetylases induces bovine leukemia virus expression in vitro and in vivo. J Virol 76: 5034-5042.
Achachi A, Florins A, Gillet N, Debacq C, Urbain P, et al. (2005) Valproate activates bovine leukemia virus gene expression, triggers apoptosis, and induces leukemia/lymphoma regression in vivo. Proc Natl Acad Sci U S A 102: 10309-10314.
Mosley AJ, Meekings KN, McCarthy C, Shepherd D, Cerundolo V, et al. (2006) Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection. Blood 108: 3801-3807.
Lezin A, Gillet N, Olindo S, Signate A, Grandvaux N, et al. (2007) Histone deacetylase mediated transcriptional activation reduces proviral loads in HTLV-1 associated myelopathy/tropical spastic paraparesis patients. Blood 110: 3722-3728.
Olindo S, Belrose G, Gillet N, Rodriguez S, Boxus M, et al. (2011) Safety of long-term treatment of HAM/TSP patients with valproic acid. Blood 118: 6306-6309.
Afonso PV, Mekaouche M, Mortreux F, Toulza F, Moriceau A, et al. (2010) Highly active antiretroviral treatment against STLV-1 infection combining reverse transcriptase and HDAC inhibitors. Blood 116: 3802-3808.
Meirom R, Moss S, Brenner J, Heller D, Trainin Z, (1997) Levels and role of cytokines in bovine leukemia virus (BLV) infection. Leukemia 11 (Suppl 3):: 219-220.
Asquith B, Mosley AJ, Barfield A, Marshall SE, Heaps A, et al. (2005) A functional CD8+ cell assay reveals individual variation in CD8+ cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load. J Gen Virol 86: 1515-1523.
Kattan T, MacNamara A, Rowan AG, Nose H, Mosley AJ, et al. (2009) The avidity and lytic efficiency of the CTL response to HTLV-1. J Immunol 182: 5723-5729.
Hilburn S, Rowan A, Demontis MA, MacNamara A, Asquith B, et al. (2011) In vivo expression of human T-lymphotropic virus type 1 basic leucine-zipper protein generates specific CD8+ and CD4+ T-lymphocyte responses that correlate with clinical outcome. J Infect Dis 203: 529-536.
Jeffery KJ, Usuku K, Hall SE, Matsumoto W, Taylor GP, et al. (1999) HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proc Natl Acad Sci U S A 96: 3848-3853.
Jeffery KJ, Siddiqui AA, Bunce M, Lloyd AL, Vine AM, et al. (2000) The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type I infection. J Immunol 165: 7278-7284.
Macnamara A, Rowan A, Hilburn S, Kadolsky U, Fujiwara H, et al. (2010) HLA class I binding of HBZ determines outcome in HTLV-1 infection. PLoS Pathog 6: e1001117.
Seich Al Basatena NK, Macnamara A, Vine AM, Thio CL, Astemborski J, et al. (2011) KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection. PLoS Pathog 7: e1002270.
Nagaoka Y, Kabeya H, Onuma M, Kasai N, Okada K, et al. (1999) Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma. Cancer Res 59: 975-981.
Juliarena MA, Poli M, Sala L, Ceriani C, Gutierrez S, et al. (2008) Association of BLV infection profiles with alleles of the BoLA-DRB3.2 gene. Anim Genet 39: 432-438.
Jensen WA, Rovnak J, Cockerell GL, (1991) In vivo transcription of the bovine leukemia virus tax/rex region in normal and neoplastic lymphocytes of cattle and sheep. J Virol 65: 2484-2490.
Kinoshita T, Shimoyama M, Tobinai K, Ito M, Ito S, et al. (1989) Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci U S A 86: 5620-5624.
Merimi M, Klener P, Szynal M, Cleuter Y, Bagnis C, et al. (2007) Complete suppression of viral gene expression is associated with the onset and progression of lymphoid malignancy: observations in Bovine Leukemia Virus-infected sheep. Retrovirology 4: 51.
Van den Broeke A, Cleuter Y, Chen G, Portetelle D, Mammerickx M, et al. (1988) Even transcriptionally competent proviruses are silent in bovine leukemia virus-induced sheep tumor cells. Proc Natl Acad Sci U S A 85: 9263-9267.
Tamiya S, Matsuoka M, Etoh K, Watanabe T, Kamihira S, et al. (1996) Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia. Blood 88: 3065-3073.
Takeda S, Maeda M, Morikawa S, Taniguchi Y, Yasunaga J, et al. (2004) Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells. Int J Cancer 109: 559-567.
Miyazaki M, Yasunaga J, Taniguchi Y, Tamiya S, Nakahata T, et al. (2007) Preferential selection of human T-cell leukemia virus type 1 provirus lacking the 5′ long terminal repeat during oncogenesis. J Virol 81: 5714-5723.
Satou Y, Yasunaga J, Yoshida M, Matsuoka M, (2006) HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. Proc Natl Acad Sci U S A 103: 720-725.
Rosewick N, Momont M, Durkin K, Takeda H, Caiment F, et al. (2013) Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia/lymphoma. Proc Natl Acad Sci U S A 110: 2306-2311.
Merimi M, Klener P, Szynal M, Cleuter Y, Kerkhofs P, et al. (2007) Suppression of viral gene expression in bovine leukemia virus-associated B-cell malignancy: interplay of epigenetic modifications leading to chromatin with a repressive histone code. J Virol 81: 5929-5939.
Kincaid RP, Burke JM, Sullivan CS, (2012) RNA virus microRNA that mimics a B-cell oncomiR. Proc Natl Acad Sci U S A 109: 3077-3082.
Berry CC, Gillet NA, Melamed A, Gormley N, Bangham CR, et al. (2012) Estimating abundances of retroviral insertion sites from DNA fragment length data. Bioinformatics 28: 755-762.
Gini (1914) Sulla misura della concentrazione e della variabilita dei caratteri: Transactions of the Real Istituto Veneto di Scienze.
Crooks GE, Hon G, Chandonia JM, Brenner SE, (2004) WebLogo: a sequence logo generator. Genome Res 14: 1188-1190.
Goecks J, Nekrutenko A, Taylor J, (2010) Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol 11: R86.
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