Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets
Abstract
:1. Introduction
2. HTLV-1 Genome and Virus Transmission and Spread
3. ATL- and HTLV-1-Driven Transformation: Generalities
4. Tax and Cell Signaling: Role of the Transcription Nuclear factor NF-κB
5. Latency and Leukemogenesis: Role of Tax, HBZ, and Apoptosis
6. Proposals for HTLV-1/ATL-Targeted Therapy
7. Potential of Gene Editing Technology in the Eradication of PersistentHTLV-1 Infection and ATL Therapy
8. Conclusions
Funding
Conflicts of Interest
References
- Gessain, A.; Cassar, O. Epidemiological aspects and world distribution of HTLV-1 infection. Front. Microbiol. 2012, 3, 388. [Google Scholar] [CrossRef] [PubMed]
- Gessain, A.; Ramassamy, J.L.; Afonso, P.V.; Cassar, O. Geographic distribution, clinical epidemiology and genetic diversity of the human oncogenic retrovirus HTLV-1 in Africa, the world’s largest endemic area. Front. Immunol. 2023, 14, 1043600. [Google Scholar] [CrossRef] [PubMed]
- Percher, F.; Jeannin, P.; Martin-Latil, S.; Gessain, A.; Afonso, P.V.; Vidy-Roche, A.; Ceccaldi, P.E. Mother-to-child transmission of HTLV-1 epidemiological aspects, mechanisms and determinants of mother-to-child transmission. Viruses 2016, 8, 40. [Google Scholar] [CrossRef] [PubMed]
- Lairmore, M.D.; Haines, R.; Anupam, R. Mechanisms of human t-lymphotropic virus type 1 transmission and disease. Curr. Opin. Virol. 2012, 2, 474–481. [Google Scholar] [CrossRef] [PubMed]
- Cook, L.B.; Melamed, A.; Demontis, M.A.; Laydon, D.J.; Fox, J.M.; Tosswill, J.H.; de Freitas, D.; Price, A.D.; Medcalf, J.F.; Martin, F.; et al. Rapid dissemination of human t-lymphotropic virus type 1 during primary infection in transplant recipients. Retrovirology 2016, 13, 3. [Google Scholar] [CrossRef]
- Nasr, R.; El Hajj, H.; Kfoury, Y.; de Thé, H.; Hermine, O.; Bazarbachi, A. Controversies in targeted therapy of adult t cell leukemia/lymphoma: On target or off target effects? Viruses 2011, 3, 750–769. [Google Scholar] [CrossRef]
- Laverdure, S.; Polakowski, N.; Hoang, K.; Lemasson, I. Permissive sense and antisense transcription from the 5’ and 3’ long terminal repeats of human t-cell leukemia virus type 1. J. Virol. 2016, 90, 3600–3610. [Google Scholar] [CrossRef]
- Fujisawa, J.; Seiki, M.; Kiyokawa, T.; Yoshida, M. Functional activation of the long terminal repeat of human t-cell leukemia virus type i by a trans-acting factor. Proc. Natl. Acad. Sci. USA 1985, 82, 2277–2281. [Google Scholar] [CrossRef]
- Boxus, M.; Willems, L. Mechanisms of HTLV-1 persistence and transformation. Br. J. Cancer 2009, 101, 1497–1501. [Google Scholar] [CrossRef]
- Baydoun, H.; Duc-Dodon, M.; Lebrun, S.; Gazzolo, L.; Bex, F. Regulation of the human t-cell leukemia virus gene expression depends on the localization of regulatory proteins tax, rex and p30ii in specific nuclear subdomains. Gene 2007, 386, 191–201. [Google Scholar] [CrossRef]
- Sarkis, S.; Galli, V.; Moles, R.; Yurick, D.; Khoury, G.; Purcell, D.F.J.; Franchini, G.; Pise-Masison, C.A. Role of HTLV-1 orf-i encoded proteins in viral transmission and persistence. Retrovirology 2019, 16, 43. [Google Scholar] [CrossRef] [PubMed]
- Silic-Benussi, M.; Marin, O.; Biasiotto, R.; D’Agostino, D.M.; Ciminale, V. Effects of human t-cell leukemia virus type 1 (HTLV-1) p13 on mitochondrial k+ permeability: A new member of the viroporin family? Febs Lett. 2010, 584, 2070–2075. [Google Scholar] [CrossRef] [PubMed]
- Younis, I.; Khair, L.; Dundr, M.; Lairmore, M.D.; Franchini, G.; Green, P.L. Repression of human t-cell leukemia virus type 1 and type 2 replication by a viral mrna-encoded posttranscriptional regulator. J. Virol. 2004, 78, 11077–11083. [Google Scholar] [CrossRef] [PubMed]
- Martin-Latil, S.; Gnadig, N.F.; Mallet, A.; Desdouits, M.; Guivel-Benhassine, F.; Jeannin, P.; Prevost, M.C.; Schwartz, O.; Gessain, A.; Ozden, S.; et al. Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells. Blood 2012, 120, 572–580. [Google Scholar] [CrossRef]
- Mulherkar, T.H.; Gomez, D.J.; Sandel, G.; Jain, P. Co-infection and cancer: Host-pathogen interaction between dendritic cells and hiv-1, HTLV-1, and other oncogenic viruses. Viruses 2022, 14, 2037. [Google Scholar] [CrossRef]
- Van Prooyen, N.; Gold, H.; Andresen, V.; Schwartz, O.; Jones, K.; Ruscetti, F.; Lockett, S.; Gudla, P.; Venzon, D.; Franchini, G. Human t-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission. Proc. Natl. Acad. Sci. USA 2010, 107, 20738–20743. [Google Scholar] [CrossRef]
- Pais-Correia, A.M.; Sachse, M.; Guadagnini, S.; Robbiati, V.; Lasserre, R.; Gessain, A.; Gout, O.; Alcover, A.; Thoulouze, M.I. Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat. Med. 2010, 16, 83–89. [Google Scholar] [CrossRef]
- Pinto, D.O.; Al Sharif, S.; Mensah, G.; Cowen, M.; Khatkar, P.; Erickson, J.; Branscome, H.; Lattanze, T.; DeMarino, C.; Alem, F.; et al. Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread. Retrovirology 2021, 18, 6. [Google Scholar] [CrossRef]
- Kim, Y.; Mensah, G.A.; Al Sharif, S.; Pinto, D.O.; Branscome, H.; Yelamanchili, S.V.; Cowen, M.; Erickson, J.; Khatkar, P.; Mahieux, R.; et al. Extracellular vesicles from infected cells are released prior to virion release. Cells 2021, 10, 781. [Google Scholar] [CrossRef]
- Overbaugh, J.; Bangham, C.R. Selection forces and constraints on retroviral sequence variation. Science 2001, 292, 1106–1109. [Google Scholar] [CrossRef]
- Laydon, D.J.; Sunkara, V.; Boelen, L.; Bangham, C.R.M.; Asquith, B. The relative contributions of infectious and mitotic spread to HTLV-1 persistence. PLoS Comput. Biol. 2020, 16, e1007470. [Google Scholar] [CrossRef] [PubMed]
- Izaki, M.; Yasunaga, J.I.; Nosaka, K.; Sugata, K.; Utsunomiya, H.; Suehiro, Y.; Shichijo, T.; Yamada, A.; Sugawara, Y.; Hibi, T.; et al. In vivo dynamics and adaptation of HTLV-1-infected clones under different clinical conditions. PLoS Pathog. 2021, 17, e1009271. [Google Scholar] [CrossRef] [PubMed]
- Fox, J.M.; Hilburn, S.; Demontis, M.A.; Brighty, D.W.; Rios Grassi, M.F.; Galvao-Castro, B.; Taylor, G.P.; Martin, F. Long terminal repeat circular DNA as markers of active viral replication of human t lymphotropic virus-1 in vivo. Viruses 2016, 8, 80. [Google Scholar] [CrossRef] [PubMed]
- Melamed, A.; Laydon, D.J.; Al Khatib, H.; Rowan, A.G.; Taylor, G.P.; Bangham, C.R. HTLV-1 drives vigorous clonal expansion of infected cd8+ t cells in natural infection. Retrovirology 2015, 12, 91. [Google Scholar] [CrossRef] [PubMed]
- Yasunaga, J. Viral, genetic, and immune factors in the oncogenesis of adult t-cell leukemia/lymphoma. Int. J. Hematol. 2023, 117, 504–511. [Google Scholar] [CrossRef]
- El Hajj, H.; Tsukasaki, K.; Cheminant, M.; Bazarbachi, A.; Watanabe, T.; Hermine, O. Novel treatments of adult t cell leukemia lymphoma. Front. Microbiol. 2020, 11, 1062. [Google Scholar] [CrossRef] [PubMed]
- Cook, L.B.; Fuji, S.; Hermine, O.; Bazarbachi, A.; Ramos, J.C.; Ratner, L.; Horwitz, S.; Fields, P.; Tanase, A.; Bumbea, H.; et al. Revised adult t-cell leukemia-lymphoma international consensus meeting report. J. Clin. Oncol. 2019, 37, 677–687. [Google Scholar] [CrossRef] [PubMed]
- Ishida, T.; Joh, T.; Uike, N.; Yamamoto, K.; Utsunomiya, A.; Yoshida, S.; Saburi, Y.; Miyamoto, T.; Takemoto, S.; Suzushima, H.; et al. Defucosylated anti-ccr4 monoclonal antibody (kw-0761) for relapsed adult t-cell leukemia-lymphoma: A multicenter phase ii study. J. Clin. Oncol. 2012, 30, 837–842. [Google Scholar] [CrossRef]
- Tanaka, T.; Inamoto, Y.; Ito, A.; Watanabe, M.; Takeda, W.; Aoki, J.; Kim, S.W.; Fukuda, T. Lenalidomide treatment for recurrent adult t-cell leukemia/lymphoma after allogeneic hematopoietic cell transplantation. Hematol. Oncol. 2022, 41, 389–395. [Google Scholar] [CrossRef] [PubMed]
- Baba, Y.; Sakai, H.; Kabasawa, N.; Harada, H. Successful treatment of an aggressive adult t-cell leukemia/lymphoma with strong cd30 expression using brentuximabvedotin as combination and maintenance therapy. Intern. Med. 2023, 62, 613–616. [Google Scholar] [CrossRef] [PubMed]
- Izutsu, K.; Makita, S.; Nosaka, K.; Yoshimitsu, M.; Utsunomiya, A.; Kusumoto, S.; Morishima, S.; Tsukasaki, K.; Kawamata, T.; Ono, T.; et al. An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult t-cell leukemia/lymphoma. Blood 2023, 141, 1159–1168. [Google Scholar] [CrossRef]
- Utsunomiya, A.; Izutsu, K.; Jo, T.; Yoshida, S.; Tsukasaki, K.; Ando, K.; Choi, I.; Imaizumi, Y.; Kato, K.; Kurosawa, M.; et al. Oral histone deacetylase inhibitor tucidinostat (hbi-8000) in patients with relapsed or refractory adult t-cell leukemia/lymphoma: Phase IIb results. Cancer Sci. 2022, 113, 2778–2787. [Google Scholar] [CrossRef] [PubMed]
- Katsuya, H. Current and emerging therapeutic strategies in adult t-cell leukemia-lymphoma. Int. J. Hematol. 2023, 117, 512–522. [Google Scholar] [CrossRef]
- Zhi, H.J.; Yang, L.P.; Kuo, Y.L.; Ho, Y.K.; Shih, H.M.; Giam, C.Z. Nf-κb hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ. PLoS Pathog. 2011, 7, e1002025. [Google Scholar] [CrossRef] [PubMed]
- Saito, K.; Saito, M.; Taniura, N.; Okuwa, T.; Ohara, Y. Activation of the pi3k-akt pathway by human t cell leukemia virus type 1 (HTLV-1) oncoprotein tax increases bcl3 expression, which is associated with enhanced growth of HTLV-1-infected t cells. Virology 2010, 403, 173–180. [Google Scholar] [CrossRef]
- Sun, S.C.; Ballard, D.W. Persistent activation of nf-κb by the tax transforming protein of HTLV-1: Hijacking cellular iκb kinases. Oncogene 1999, 18, 6948–6958. [Google Scholar] [CrossRef]
- Shimotohno, K.; Takano, M.; Teruuchi, T.; Miwa, M. Requirement of multiple copies of a 21-nucleotide sequence in the u3 regions of human t-cell leukemia virus type I and type II long terminal repeats for trans-acting activation of transcription. Proc. Natl. Acad. Sci. USA 1986, 83, 8112–8116. [Google Scholar] [CrossRef] [PubMed]
- Giam, C.Z.; Xu, Y.L. HTLV-i tax gene product activates transcription via pre-existing cellular factors and camp responsive element. J. Biol. Chem. 1989, 264, 15236–15241. [Google Scholar] [CrossRef] [PubMed]
- Adya, N.; Giam, C.Z. Distinct regions in human t-cell lymphotropic virus type I tax mediate interactions with activator protein creb and basal transcription factors. J. Virol. 1995, 69, 1834–1841. [Google Scholar] [CrossRef] [PubMed]
- Lenzmeier, B.A.; Giebler, H.A.; Nyborg, J.K. Human t-cell leukemia virus type 1 tax requires direct access to DNA for recruitment of creb binding protein to the viral promoter. Mol. Cell Biol. 1998, 18, 721–731. [Google Scholar] [CrossRef] [PubMed]
- Kimzey, A.L.; Dynan, W.S. Specific regions of contact between human t-cell leukemia virus type i tax protein and DNA identified by photocross-linking. J. Biol. Chem. 1998, 273, 13768–13775. [Google Scholar] [CrossRef]
- Lu, H.; Pise-Masison, C.A.; Linton, R.; Park, H.U.; Schiltz, R.L.; Sartorelli, V.; Brady, J.N. Tax relieves transcriptional repression by promoting histone deacetylase 1 release from the human t-cell leukemia virus type 1 long terminal repeat. J. Virol. 2004, 78, 6735–6743. [Google Scholar] [CrossRef] [PubMed]
- Ego, T.; Ariumi, Y.; Shimotohno, K. The interaction of HTLV-1 tax with hdac1 negatively regulates the viral gene expression. Oncogene 2002, 21, 7241–7246. [Google Scholar] [CrossRef] [PubMed]
- Mitchell, S.; Vargas, J.; Hoffmann, A. Signaling via the nfκb system. Wiley Interdiscip. Rev. Syst. Biol. Med. 2016, 8, 227–241. [Google Scholar] [CrossRef]
- Kanno, T.; Brown, K.; Franzoso, G.; Siebenlist, U. Kinetic analysis of human t-cell leukemia virus type i tax-mediated activation of nf-κb. Mol. Cell Biol. 1994, 14, 6443–6451. [Google Scholar] [CrossRef] [PubMed]
- Geleziunas, R.; Ferrell, S.; Lin, X.; Mu, Y.; Cunningham, E.T., Jr.; Grant, M.; Connelly, M.A.; Hambor, J.E.; Marcu, K.B.; Greene, W.C. Human t-cell leukemia virus type 1 tax induction of nf-κb involves activation of the iκb kinase α (ikkα) and ikkβ cellular kinases. Mol. Cell Biol. 1998, 18, 5157–5165. [Google Scholar] [CrossRef]
- Fuggetta, M.P.; Bordignon, V.; Cottarelli, A.; Macchi, B.; Frezza, C.; Cordiali-Fei, P.; Ensoli, F.; Ciafre, S.; Marino-Merlo, F.; Mastino, A.; et al. Downregulation of proinflammatory cytokines in HTLV-1-infected t cells by resveratrol. J. Exp. Clin. Cancer Res. 2016, 35, 118. [Google Scholar] [CrossRef]
- Mohanty, S.; Harhaj, E.W. Mechanisms of oncogenesis by HTLV-1 tax. Pathogens 2020, 9, 543. [Google Scholar] [CrossRef]
- Hleihel, R.; Skayneh, H.; de The, H.; Hermine, O.; Bazarbachi, A. Primary cells from patients with adult t cell leukemia/lymphoma depend on HTLV-1 tax expression for nf-κb activation and survival. Blood Cancer J. 2023, 13, 67. [Google Scholar] [CrossRef] [PubMed]
- Macaire, H.; Riquet, A.; Moncollin, V.; Biemont-Trescol, M.C.; DucDodon, M.; Hermine, O.; Debaud, A.L.; Mahieux, R.; Mesnard, J.M.; Pierre, M.; et al. Tax protein-induced expression of antiapoptotic bfl-1 protein contributes to survival of human t-cell leukemia virus type 1 (HTLV-1)-infected t-cells. J. Biol. Chem. 2012, 287, 21357–21370. [Google Scholar] [CrossRef] [PubMed]
- Kawakami, H.; Tomita, M.; Matsuda, T.; Ohta, T.; Tanaka, Y.; Fujii, M.; Hatano, M.; Tokuhisa, T.; Mori, N. Transcriptional activation of survivin through the nf-κb pathway by human t-cell leukemia virus type I Tax. Int. J. Cancer 2005, 115, 967–974. [Google Scholar] [CrossRef] [PubMed]
- Kogure, Y.; Kataoka, K. Genetic alterations in adult t-cell leukemia/lymphoma. Cancer Sci. 2017, 108, 1719–1725. [Google Scholar] [CrossRef] [PubMed]
- Jo, T.; Noguchi, K.; Sakai, T.; Kubota-Koketsu, R.; Irie, S.; Matsuo, M.; Taguchi, J.; Abe, K.; Shigematsu, K. HTLV-1 tax-specific memory cytotoxic t lymphocytes in long-term survivors of aggressive-type adult t-cell leukemia/lymphoma. Cancer Med. 2022, 11, 3238–3250. [Google Scholar] [CrossRef] [PubMed]
- Yasunaga, J.I. Strategies of human t-cell leukemia virus type 1 for persistent infection: Implications for leukemogenesis of adult t-cell leukemia-lymphoma. Front. Microbiol. 2020, 11, 979. [Google Scholar] [CrossRef] [PubMed]
- Akkouche, A.; Moodad, S.; Hleihel, R.; Skayneh, H.; Chambeyron, S.; El Hajj, H.; Bazarbachi, A. In vivo antagonistic role of the human t-cell leukemia virus type 1 regulatory proteins tax and hbz. PLoS Pathog. 2021, 17, e1009219. [Google Scholar] [CrossRef]
- Arnold, J.; Yamamoto, B.; Li, M.; Phipps, A.J.; Younis, I.; Lairmore, M.D.; Green, P.L. Enhancement of infectivity and persistence in vivo by hbz, a natural antisense coded protein of HTLV-1. Blood 2006, 107, 3976–3982. [Google Scholar] [CrossRef] [PubMed]
- Gazon, H.; Lemasson, I.; Polakowski, N.; Cesaire, R.; Matsuoka, M.; Barbeau, B.; Mesnard, J.M.; Peloponese, J.M., Jr. Human t-cell leukemia virus type 1 (HTLV-1) bzip factor requires cellular transcription factor jund to upregulate HTLV-1 antisense transcription from the 3’ long terminal repeat. J. Virol. 2012, 86, 9070–9078. [Google Scholar] [CrossRef]
- Vernin, C.; Thenoz, M.; Pinatel, C.; Gessain, A.; Gout, O.; Delfau-Larue, M.H.; Nazaret, N.; Legras-Lachuer, C.; Wattel, E.; Mortreux, F. HTLV-1 bzip factor hbz promotes cell proliferation and genetic instability by activating oncomirs. Cancer Res. 2014, 74, 6082–6093. [Google Scholar] [CrossRef]
- Rushing, A.W.; Hoang, K.; Polakowski, N.; Lemasson, I. The human t-cell leukemia virus type 1 basic leucine zipper factor attenuates repair of double-stranded DNA breaks via nonhomologous end joining. J. Virol. 2018, 92, e00672. [Google Scholar] [CrossRef]
- Sakurada-Aono, M.; Sakamoto, T.; Kobayashi, M.; Takiuchi, Y.; Iwai, F.; Tada, K.; Sasanuma, H.; Hirabayashi, S.; Murakawa, Y.; Shirakawa, K.; et al. HTLV-1 bzip factor impairs DNA mismatch repair system. Biochem. Biophys. Res. Commun. 2023, 657, 43–49. [Google Scholar] [CrossRef] [PubMed]
- Forlani, G.; Shallak, M.; Tedeschi, A.; Cavallari, I.; Marcais, A.; Hermine, O.; Accolla, R.S. Dual cytoplasmic and nuclear localization of HTLV-1-encoded hbz protein is a unique feature of adult t-cell leukemia. Haematologica 2021, 106, 2076–2085. [Google Scholar] [CrossRef] [PubMed]
- Tanaka-Nakanishi, A.; Yasunaga, J.; Takai, K.; Matsuoka, M. HTLV-1 bzip factor suppresses apoptosis by attenuating the function of foxo3a and altering its localization. Cancer Res. 2014, 74, 188–200. [Google Scholar] [CrossRef] [PubMed]
- Mitobe, Y.; Yasunaga, J.; Furuta, R.; Matsuoka, M. HTLV-1 bzip factor rna and protein impart distinct functions on t-cell proliferation and survival. Cancer Res. 2015, 75, 4143–4152. [Google Scholar] [CrossRef]
- Nicot, C.; Dundr, M.; Johnson, J.M.; Fullen, J.R.; Alonzo, N.; Fukumoto, R.; Princler, G.L.; Derse, D.; Misteli, T.; Franchini, G. HTLV-1-encoded p30ii is a post-transcriptional negative regulator of viral replication. Nat. Med. 2004, 10, 197–201. [Google Scholar] [CrossRef] [PubMed]
- Silic-Benussi, M.; Cavallari, I.; Vajente, N.; Vidali, S.; Chieco-Bianchi, L.; Di Lisa, F.; Saggioro, D.; D’Agostino, D.M.; Ciminale, V. Redox regulation of t-cell turnover by the p13 protein of human t-cell leukemia virus type 1: Distinct effects in primary versus transformed cells. Blood 2010, 116, 54–62. [Google Scholar] [CrossRef] [PubMed]
- Nicot, C.; Mulloy, J.C.; Ferrari, M.G.; Johnson, J.M.; Fu, K.; Fukumoto, R.; Trovato, R.; Fullen, J.; Leonard, W.J.; Franchini, G. HTLV-1 p12(i) protein enhances stat5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells. Blood 2001, 98, 823–829. [Google Scholar] [CrossRef] [PubMed]
- Gazon, H.; Chauhan, P.S.; Porquet, F.; Hoffmann, G.B.; Accolla, R.; Willems, L. Epigenetic silencing of HTLV-1 expression by the hbzrna through interference with the basal transcription machinery. Blood Adv. 2020, 4, 5574–5579. [Google Scholar] [CrossRef] [PubMed]
- Gaudray, G.; Gachon, F.; Basbous, J.; Biard-Piechaczyk, M.; Devaux, C.; Mesnard, J.M. The complementary strand of the human t-cell leukemia virus type 1 rna genome encodes a bzip transcription factor that down-regulates viral transcription. J. Virol. 2002, 76, 12813–12822. [Google Scholar] [CrossRef] [PubMed]
- Clerc, I.; Polakowski, N.; Andre-Arpin, C.; Cook, P.; Barbeau, B.; Mesnard, J.M.; Lemasson, I. An interaction between the human t cell leukemia virus type 1 basic leucine zipper factor (hbz) and the kix domain of p300/cbp contributes to the down-regulation of tax-dependent viral transcription by hbz. J. Biol. Chem. 2008, 283, 23903–23913. [Google Scholar] [CrossRef] [PubMed]
- Kiik, H.; Ramanayake, S.; Miura, M.; Tanaka, Y.; Melamed, A.; Bangham, C.R.M. Time-course of host cell transcription during the HTLV-1 transcriptional burst. PLoS Pathog. 2022, 18, e1010387. [Google Scholar] [CrossRef] [PubMed]
- Copeland, K.F.; Haaksma, A.G.; Goudsmit, J.; Krammer, P.H.; Heeney, J.L. Inhibition of apoptosis in t cells expressing human t cell leukemia virus type I Tax. AIDS Res. Hum. Retrovir. 1994, 10, 1259–1268. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.C.; Hsu, T.Y.; Lin, R.H.; Su, I.J.; Chen, J.Y.; Yang, C.S. Resistance to tumor necrosis factor-α-induced apoptosis in human t-lymphotropic virus type i-infected t cell lines. AIDS Res. Hum. Retrovir. 2002, 18, 207–212. [Google Scholar] [CrossRef]
- Brauweiler, A.; Garrus, J.E.; Reed, J.C.; Nyborg, J.K. Repression of bax gene expression by the HTLV-1 tax protein: Implications for suppression of apoptosis in virally infected cells. Virology 1997, 231, 135–140. [Google Scholar] [CrossRef]
- Mori, N.; Fujii, M.; Cheng, G.; Ikeda, S.; Yamasaki, Y.; Yamada, Y.; Tomonaga, M.; Yamamoto, N. Human t-cell leukemia virus type i tax protein induces the expression of anti-apoptotic gene bcl-xl in human t-cells through nuclear factor-κb and c-amp responsive element binding protein pathways. Virus Genes. 2001, 22, 279–287. [Google Scholar] [CrossRef] [PubMed]
- Chlichlia, K.; Moldenhauer, G.; Daniel, P.T.; Busslinger, M.; Gazzolo, L.; Schirrmacher, V.; Khazaie, K. Immediate effects of reversible HTLV-1 tax function: T-cell activation and apoptosis. Oncogene 1995, 10, 269–277. [Google Scholar]
- Chlichlia, K.; Busslinger, M.; Peter, M.E.; Walczak, H.; Krammer, P.H.; Schirrmacher, V.; Khazaie, K. Ice-proteases mediate HTLV-i tax-induced apoptotic t-cell death. Oncogene 1997, 14, 2265–2272. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Zachar, V.; Zdravkovic, M.; Guo, M.; Ebbesen, P.; Liu, X. Role of the fas/fas ligand pathway in apoptotic cell death induced by the human t cell lymphotropic virus type i tax transactivator. J. Gen. Virol. 1997, 78 Pt 12, 3277–3285. [Google Scholar] [CrossRef]
- Nicot, C.; Harrod, R. Distinct p300-responsive mechanisms promote caspase-dependent apoptosis by human t-cell lymphotropic virus type 1 tax protein. Mol. Cell Biol. 2000, 20, 8580–8589. [Google Scholar] [CrossRef] [PubMed]
- Rivera-Walsh, I.; Waterfield, M.; Xiao, G.; Fong, A.; Sun, S.C. Nf-κb signaling pathway governs trail gene expression and human t-cell leukemia virus-i tax-induced t-cell death. J. Biol. Chem. 2001, 276, 40385–40388. [Google Scholar] [CrossRef]
- Matteucci, C.; Balestrieri, E.; Macchi, B.; Mastino, A. Modulation of apoptosis during HTLV-1-mediated immortalization process in vitro. J. Med. Virol. 2004, 74, 473–483. [Google Scholar] [CrossRef]
- Mahgoub, M.; Yasunaga, J.I.; Iwami, S.; Nakaoka, S.; Koizumi, Y.; Shimura, K.; Matsuoka, M. Sporadic on/off switching of HTLV-1 tax expression is crucial to maintain the whole population of virus-induced leukemic cells. Proc. Natl. Acad. Sci. USA 2018, 115, E1269–E1278. [Google Scholar] [CrossRef] [PubMed]
- Shudofsky, A.M.D.; Giam, C.Z. Cells of adult t-cell leukemia evade HTLV-1 tax/nf-κb hyperactivation-induced senescence. Blood Adv. 2019, 3, 564–569. [Google Scholar] [CrossRef] [PubMed]
- Ramanayake, S.; Moulding, D.A.; Tanaka, Y.; Singh, A.; Bangham, C.R.M. Dynamics and consequences of the HTLV-1 proviral plus-strand burst. PLoS Pathog. 2022, 18, e1010774. [Google Scholar] [CrossRef] [PubMed]
- Abou-Kandil, A.; Chamias, R.; Huleihel, M.; Godbey, W.T.; Aboud, M. Role of caspase 9 in activation of HTLV-1 ltr expression by DNA damaging agents. Cell Cycle 2011, 10, 3337–3345. [Google Scholar] [CrossRef] [PubMed]
- Kulkarni, A.; Mateus, M.; Thinnes, C.C.; McCullagh, J.S.; Schofield, C.J.; Taylor, G.P.; Bangham, C.R.M. Glucose metabolism and oxygen availability govern reactivation of the latent human retrovirus HTLV-1. Cell Chem. Biol. 2017, 24, 1377–1387.e3. [Google Scholar] [CrossRef] [PubMed]
- Sales, D.; Lin, E.; Stoffel, V.; Dickson, S.; Khan, Z.K.; Beld, J.; Jain, P. Apigenin improves cytotoxicity of antiretroviral drugs against HTLV-1 infected cells through the modulation of ahr signaling. NeuroImmune Pharm. Ther. 2023, 2, 49–62. [Google Scholar] [CrossRef]
- Sato, T.; Maeta, T.; Ito, S. Dimethyl fumarate suppresses the proliferation of HTLV-1-infected t cells by inhibiting cbm complex-triggered nf-κb signaling. Anticancer. Res. 2023, 43, 1901–1908. [Google Scholar] [CrossRef] [PubMed]
- Thorpe, L.M.; Yuzugullu, H.; Zhao, J.J. Pi3k in cancer: Divergent roles of isoforms, modes of activation and therapeutic targeting. Nat. Rev. Cancer 2015, 15, 7–24. [Google Scholar] [CrossRef]
- Hemmati, S.; Sinclair, T.; Tong, M.; Bartholdy, B.; Okabe, R.O.; Ames, K.; Ostrodka, L.; Haque, T.; Kaur, I.; Mills, T.S.; et al. Pi3k alpha and delta promote hematopoietic stem cell activation. JCI Insight 2019, 4, e125832. [Google Scholar] [CrossRef] [PubMed]
- Fukuda, R.; Hayashi, A.; Utsunomiya, A.; Nukada, Y.; Fukui, R.; Itoh, K.; Tezuka, K.; Ohashi, K.; Mizuno, K.; Sakamoto, M.; et al. Alteration of phosphatidylinositol 3-kinase cascade in the multilobulated nuclear formation of adult t cell leukemia/lymphoma (atll). Proc. Natl. Acad. Sci. USA 2005, 102, 15213–15218. [Google Scholar] [CrossRef] [PubMed]
- Katsuya, H.; Cook, L.B.M.; Rowan, A.G.; Satou, Y.; Taylor, G.P.; Bangham, C.R.M. Phosphatidylinositol 3-kinase-delta (pi3k-delta) is a potential therapeutic target in adult t-cell leukemia-lymphoma. Biomark. Res. 2018, 6, 24. [Google Scholar] [CrossRef] [PubMed]
- Ishikawa, C.; Mori, N. The role of cudc-907, a dual phosphoinositide-3 kinase and histone deacetylase inhibitor, in inhibiting proliferation of adult t-cell leukemia. Eur. J. Haematol. 2020, 105, 763–772. [Google Scholar] [CrossRef]
- Ishikawa, C.; Senba, M.; Mori, N. Butein inhibits nf-κb, ap-1 and akt activation in adult t-cell leukemia/lymphoma. Int. J. Oncol. 2017, 51, 633–643. [Google Scholar] [CrossRef]
- Matteucci, C.; Marino-Merlo, F.; Minutolo, A.; Balestrieri, E.; Valletta, E.; Macchi, B.; Mastino, A.; Grelli, S. Inhibition of iκbα phosphorylation potentiates regulated cell death induced by azidothymidine in HTLV-1 infected cells. Cell Death Discov. 2020, 6, 9. [Google Scholar] [CrossRef] [PubMed]
- Migone, T.S.; Lin, J.X.; Cereseto, A.; Mulloy, J.C.; O’Shea, J.J.; Franchini, G.; Leonard, W.J. Constitutively activated jak-stat pathway in t cells transformed with HTLV-1. Science 1995, 269, 79–81. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Mathews Griner, L.A.; Ju, W.; Duveau, D.Y.; Guha, R.; Petrus, M.N.; Wen, B.; Maeda, M.; Shinn, P.; Ferrer, M.; et al. Selective targeting of jak/stat signaling is potentiated by bcl-xl blockade in il-2-dependent adult t-cell leukemia. Proc. Natl. Acad. Sci. USA 2015, 112, 12480–12485. [Google Scholar] [CrossRef] [PubMed]
- Daenthanasanmak, A.; Bamford, R.N.; Yoshioka, M.; Yang, S.M.; Homan, P.; Karim, B.; Bryant, B.R.; Petrus, M.N.; Thomas, C.J.; Green, P.L.; et al. Triple combination of bet plus pi3k and nf-κb inhibitors exhibit synergistic activity in adult t-cell leukemia/lymphoma. Blood Adv. 2022, 6, 2346–2360. [Google Scholar] [CrossRef] [PubMed]
- Macchi, B.; Balestrieri, E.; Frezza, C.; Grelli, S.; Valletta, E.; Marcais, A.; Marino-Merlo, F.; Turpin, J.; Bangham, C.R.; Hermine, O.; et al. Quantification of HTLV-1 reverse transcriptase activity in atl patients treated with zidovudine and interferon-α. Blood Adv. 2017, 1, 748–752. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Yu, J.; Cheng, S.; Zhang, Y.; Zhou, C.H.; Qin, J.; Luo, H. Research progress on the anticancer molecular mechanism of targets regulating cell autophagy. Pharmacology 2023, 108, 224–237. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.; Liu, D.; Zhang, Y.; Zhang, H.; Cheng, H. The autophagy molecule beclin 1 maintains persistent activity of nf-κb and stat3 in HTLV-1-transformed t lymphocytes. Biochem. Biophys. Res. Commun. 2015, 465, 739–745. [Google Scholar] [CrossRef]
- Fauzi, Y.R.; Nakahata, S.; Chilmi, S.; Ichikawa, T.; Nueangphuet, P.; Yamaguchi, R.; Nakamura, T.; Shimoda, K.; Morishita, K. Antitumor effects of chloroquine/hydroxychloroquine mediated by inhibition of the nf-κb signaling pathway through abrogation of autophagic p47 degradation in adult t-cell leukemia/lymphoma cells. PLoS ONE 2021, 16, e0256320. [Google Scholar] [CrossRef] [PubMed]
- Kozako, T.; Mellini, P.; Ohsugi, T.; Aikawa, A.; Uchida, Y.I.; Honda, S.I.; Suzuki, T. Novel small molecule sirt2 inhibitors induce cell death in leukemic cell lines. BMC Cancer 2018, 18, 791. [Google Scholar] [CrossRef] [PubMed]
- Machado, C.B.; da Cunha, L.S.; Maues, J.H.D.; Pessoa, F.M.C.D.; de Oliveira, M.B.; Ribeiro, R.M.; Lopes, G.S.; de Moraes, M.O.; de Moraes, M.E.A.; Khayat, A.S.; et al. Role of MIRANs in human t cell leukemia virus type 1 induced t cell leukemia: A literature review and bioinformatics approach. Int. J. Mol. Sci. 2022, 23, 5486. [Google Scholar] [CrossRef] [PubMed]
- Schnell, A.P.; Kohrt, S.; Aristodemou, A.; Taylor, G.P.; Bangham, C.R.M.; Thoma-Kress, A.K. Hdac inhibitors panobinostat and romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients’ t-cells. Front. Immunol. 2022, 13, 978800. [Google Scholar] [CrossRef] [PubMed]
- Huang, J.; Cook, D.E. The contribution of DNA repair pathways to genome editing and evolution in filamentous pathogens. FEMS Microbiol. Rev. 2022, 46, fuac035. [Google Scholar] [CrossRef]
- Xue, C.; Greene, E.C. DNA repair pathway choices in crispr-cas9-mediated genome editing. Trends Genet. 2021, 37, 639–656. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, A.; Takeda, S.; Kariya, R.; Matsuda, K.; Urano, E.; Okada, S.; Komano, J. A novel therapeutic molecule against HTLV-1 infection targeting provirus. Leukemia 2013, 27, 1621–1627. [Google Scholar] [CrossRef]
- Rojo-Romanos, T.; Karpinski, J.; Millen, S.; Beschorner, N.; Simon, F.; Paszkowski-Rogacz, M.; Lansing, F.; Schneider, P.M.; Sonntag, J.; Hauber, J.; et al. Precise excision of HTLV-1 provirus with a designer-recombinase. Mol. Ther. 2023, 31, 2266–2285. [Google Scholar] [CrossRef] [PubMed]
- Nakagawa, M.; Shaffer, A.L., 3rd; Ceribelli, M.; Zhang, M.; Wright, G.; Huang, D.W.; Xiao, W.; Powell, J.; Petrus, M.N.; Yang, Y.; et al. Targeting the HTLV-I-regulated BATF3/IRF4 transcriptional network in adult t cell leukemia/lymphoma. Cancer Cell 2018, 34, 286–297.e210. [Google Scholar] [CrossRef] [PubMed]
- Panfil, A.R.; Green, P.L.; Yoder, K.E. Crispr genome editing applied to the pathogenic retrovirus HTLV-1. Front. Cell Infect. Microbiol. 2020, 10, 580371. [Google Scholar] [CrossRef] [PubMed]
- Kaminski, R.; Chen, Y.; Fischer, T.; Tedaldi, E.; Napoli, A.; Zhang, Y.; Karn, J.; Hu, W.; Khalili, K. Corrigendum: Elimination of hiv-1 genomes from human t-lymphoid cells by crispr/cas9 gene editing. Sci. Rep. 2016, 6, 28213. [Google Scholar] [CrossRef] [PubMed]
- Xiao, Q.; Guo, D.; Chen, S. Application of crispr/cas9-based gene editing in hiv-1/aids therapy. Front. Cell Infect. Microbiol. 2019, 9, 69. [Google Scholar] [CrossRef] [PubMed]
- Lai, M.; Maori, E.; Quaranta, P.; Matteoli, G.; Maggi, F.; Sgarbanti, M.; Crucitta, S.; Pacini, S.; Turriziani, O.; Antonelli, G.; et al. Crispr/cas9 ablation of integrated hiv-1 accumulates proviral DNA circles with reformed long terminal repeats. J. Virol. 2021, 95, e0135821. [Google Scholar] [CrossRef] [PubMed]
Proposed Therapeutic Treatment | Target | Available Results | ||
---|---|---|---|---|
Viral | Cellular | In Vitro/Ex Vivo | In Vivo | |
AZT + IFNα (98) | RT | IFN-receptor other? 1 | Samples from patients: (a) Complete inhibition of RT activity and (b) reduction in virus parameters in responding patients; (c) Dramatic change in the clonality pattern. | Prolonged survival with respect to untreated patients |
Idelalisib (91) | ? | PI3K-δ/AKT | Inhibition of proliferation in ATL cells. | No |
CUDC-907 (92) | ? | PI3K/HDAC | (a) Induction of cytotoxicity in HTLV-1-infected cells; (b) Inhibition of HSP90 activity; (c) Increased caspase activity in ATL cells. | No |
Butein (93) | ? | AKT/AP1 NF-kB | (a) Induction of apoptosis; (b) Inhibition of proliferation of HTLV-1-infected and ATL cells. | No |
AZT+ Bay 11-7085 (94) | RT- | IκBα phosphorylation | (a) Increased apoptosis; (b) Up-reg. pro-apoptotic and down-reg. anti- apoptotic genes in HTLV-1-infected/transformed cells. | No |
Ruxolitinib+ Navitoclax (96) | ? | JAK/STAT Bcl-2/Bcl-xL | Cytotoxicity in IL-2-dependent ATL cell lines and ex vivo in lymphocytes from ATL patients. | No |
I-BET762+ Copanlisib+ bardoxolone methyl (97) | ? | BET NF-κB PI3K | Inhibition of proliferation in ATL cells in vitro and ex vivo samples from patients. | Prolonged survival of ATL-bearing xenograft mice |
Chloroquine/ Hydroxy chloroquine (101) | ? | Autophagic flux | Ex vivo from ATL patients: (a) Inhibition of autophagy; (b) Accumulation of p47 with LC3IIand inhibition of NF-κB activation; (c) Proneness to apoptosis. | No |
NCO-90/141 (102) | ? | Sirtuin 2 | (a) Increased apoptosis; (b) Autophagy in ATL cells. | No |
? (103) | ? | 12 miRNA | In silico analysis identified 12 miRNA deregulated in HTLV-1 samples predicted to interact with 90 genes. | No |
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Marino-Merlo, F.; Grelli, S.; Mastino, A.; Lai, M.; Ferrari, P.; Nicolini, A.; Pistello, M.; Macchi, B. Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets. Int. J. Mol. Sci. 2023, 24, 14807. https://doi.org/10.3390/ijms241914807
Marino-Merlo F, Grelli S, Mastino A, Lai M, Ferrari P, Nicolini A, Pistello M, Macchi B. Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets. International Journal of Molecular Sciences. 2023; 24(19):14807. https://doi.org/10.3390/ijms241914807
Chicago/Turabian StyleMarino-Merlo, Francesca, Sandro Grelli, Antonio Mastino, Michele Lai, Paola Ferrari, Andrea Nicolini, Mauro Pistello, and Beatrice Macchi. 2023. "Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets" International Journal of Molecular Sciences 24, no. 19: 14807. https://doi.org/10.3390/ijms241914807