Human T cell leukemia virus type 1 and Zika virus: tale of two reemerging viruses with neuropathological sequelae of public health concern

  • DeGaulle I. Chigbu
  • Pooja Jain
  • Brenndan L. Crumley
  • Dip Patel
  • Zafar K. KhanEmail author


Human T cell leukemia virus type 1 (HTLV-1) and Zika virus (ZIKV) have been considered neglected viruses of low public health concern until recently when incidences of HTLV-1 and ZIKV were observed to be linked to serious immune-related disease and neurological complications. This review will discuss the epidemiology, genomic evolution, virus-host interactions, virulence factors, neuropathological sequelae, and current perspectives of these reemerging viruses. There are no FDA-approved therapeutics or vaccines against these viruses, and as such, it is important for clinical trials to focus on developing vaccines that can induce cell-mediated immune response to confer long-term protective immunity. Furthermore, attention should be paid to reducing the transmission of these viruses through unprotected sex, infected blood during sharing of contaminated needles, donated blood and organs, and vertical transmission from mother to baby via breastfeeding. There is an urgent need to re-evaluate repurposing current antiviral therapies as well as developing novel antiviral agents with enhanced efficacy due to the high morbidity rate associated with these two reemerging chronic viral diseases.


HTLV Zika virus HAM/TSP GBS Microcephaly 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Acosta-Ampudia Y, Monsalve DM, Castillo-Medina LF, Rodriguez Y, Pacheco Y, Halstead S et al (2018) Autoimmune neurological conditions associated with Zika virus infection. Front Mol Neurosci 11:116CrossRefPubMedPubMedCentralGoogle Scholar
  2. Akiyama BM, Laurence HM, Massey AR, Costantino DA, Xie X, Yang Y, Shi PY, Nix JC, Beckham JD, Kieft JS (2016) Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease. Science 354(6316):1148–1152CrossRefPubMedPubMedCentralGoogle Scholar
  3. Alefantis T, Jain P, Ahuja J, Mostoller K, Wigdahl B (2005) HTLV-1 Tax nucleocytoplasmic shuttling, interaction with the secretory pathway, extracellular signaling, and implications for neurologic disease. J Biomed Sci 12(6):961–974CrossRefPubMedGoogle Scholar
  4. Alefantis T, Flaig KE, Wigdahl B, Jain P (2007) Interaction of HTLV-1 Tax protein with calreticulin: implications for Tax nuclear export and secretion. Biomed Pharmacother 61(4):194–200CrossRefPubMedPubMedCentralGoogle Scholar
  5. Aliya N, Rahman S, Khan ZK, Jain P (2012) Cotranscriptional chromatin remodeling by small RNA species: an HTLV-1 perspective. Leuk Res Treatment 2012:984754PubMedPubMedCentralGoogle Scholar
  6. Alphey L, McKemey A, Nimmo D, Neira Oviedo M, Lacroix R, Matzen K, Beech C (2013) Genetic control of Aedes mosquitoes. Pathog Glob Health 107(4):170–179CrossRefPubMedPubMedCentralGoogle Scholar
  7. Andrade RG, Goncalves Pde C, Ribeiro MA, Romanelli LC, Ribas JG, Torres EB et al (2013) Strong correlation between tax and HBZ mRNA expression in HAM/TSP patients: distinct markers for the neurologic disease. J Clin Virol 56(2):135–140CrossRefPubMedGoogle Scholar
  8. Araujo AQ, Silva MT (2006) The HTLV-1 neurological complex. J Acquir Immune Defic Syndr 5(12):1068–1076Google Scholar
  9. Atif M, Azeem M, Sarwar MR, Bashir A (2016) Zika virus disease: a current review of the literature. Infection 44(6):695–705CrossRefPubMedGoogle Scholar
  10. Azimi N, Brown K, Bamford RN, Tagaya Y, Siebenlist U, Waldmann TA (1998) Human T cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NF-kappaB site. Proc Natl Acad Sci U S A 95(5):2452–2457CrossRefPubMedPubMedCentralGoogle Scholar
  11. Azimi N, Jacobson S, Leist T, Waldmann TA (1999) Involvement of IL-15 in the pathogenesis of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis: implications for therapy with a monoclonal antibody directed to the IL-2/15R beta receptor. J Immunol 163(7):4064–4072PubMedGoogle Scholar
  12. Bai XT, Nicot C (2012) Overview on HTLV-1 p12, p8, p30, p13: accomplices in persistent infection and viral pathogenesis. Front Microbiol 3:400CrossRefPubMedPubMedCentralGoogle Scholar
  13. Balmaseda A, Zambrana JV, Collado D, Garcia N, Saborio S, Elizondo D, et al. Comparison of four serological methods and two reverse transcription-PCR assays for diagnosis and surveillance of Zika virus infection. J Clin Microbiol. 2018;56(3)Google Scholar
  14. Bangham CRM, Matsuoka M. Human T-cell leukaemia virus type 1: parasitism and pathogenesis. Philos Trans R Soc Lond Ser B Biol Sci 2017;372(1732)Google Scholar
  15. Barbeau B, Peloponese JM, Mesnard JM. Functional comparison of antisense proteins of HTLV-1 and HTLV-2 in viral pathogenesis. Front Microbiol 2013;4Google Scholar
  16. Barouch DH, Thomas SJ, Michael NL (2017) Prospects for a Zika virus vaccine. Immunity 46(2):176–182CrossRefPubMedPubMedCentralGoogle Scholar
  17. Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Marques ET Jr et al (2016) Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe 19(5):705–712CrossRefPubMedPubMedCentralGoogle Scholar
  18. Bayless NL, Greenberg RS, Swigut T, Wysocka J, Blish CA (2016) Zika virus infection induces cranial neural crest cells to produce cytokines at levels detrimental for neurogenesis. Cell Host Microbe 20(4):423–428CrossRefPubMedPubMedCentralGoogle Scholar
  19. Calvet G, Aguiar RS, Melo ASO, Sampaio SA, de Filippis I, Fabri A, Araujo ESM, de Sequeira PC, de Mendonça MCL, de Oliveira L, Tschoeke DA, Schrago CG, Thompson FL, Brasil P, dos Santos FB, Nogueira RMR, Tanuri A, de Filippis AMB (2016) Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis 16(6):653–660CrossRefPubMedGoogle Scholar
  20. Catalan-Soares BC, Carneiro-Proietti AB, Da Fonseca FG, Correa-Oliveira R, Peralva-Lima D, Portela R et al (2009) HLA class I alleles in HTLV-1-associated myelopathy and asymptomatic carriers from the Brazilian cohort GIPH. Med Microbiol Immunol 198(1):1–3CrossRefPubMedGoogle Scholar
  21. Chen YM, Okayama A, Lee TH, Tachibana N, Mueller N, Essex M (1991) Sexual transmission of human T-cell leukemia virus type I associated with the presence of anti-Tax antibody. Proc Natl Acad Sci U S A 88(4):1182–1186CrossRefPubMedPubMedCentralGoogle Scholar
  22. Colisson R, Barblu L, Gras C, Raynaud F, Hadj-Slimane R, Pique C, Hermine O, Lepelletier Y, Herbeuval JP (2010) Free HTLV-1 induces TLR7-dependent innate immune response and TRAIL relocalization in killer plasmacytoid dendritic cells. Blood 115(11):2177–2185CrossRefPubMedGoogle Scholar
  23. Cook LBM, Taylor GP (2014) HTLV-1 and HTLV-2 prevalence in the United States. J Infect Dis 209(4):486–487CrossRefPubMedGoogle Scholar
  24. Cook LB, Melamed A, Demontis MA, Laydon DJ, Fox JM, Tosswill JH et al (2016) Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients. Retrovirology 13:3CrossRefPubMedPubMedCentralGoogle Scholar
  25. Cross SL, Feinberg MB, Wolf JB, Holbrook NJ, Wong-Staal F, Leonard WJ (1987) Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cell 49(1):47–56CrossRefPubMedGoogle Scholar
  26. Culshaw A, Mongkolsapaya J, Screaton GR (2017) The immunopathology of dengue and Zika virus infections. Curr Opin Immunol 48:1–6CrossRefPubMedGoogle Scholar
  27. Culshaw A, Mongkolsapaya J, Screaton G (2018) The immunology of Zika virus. F1000Res 7:203CrossRefPubMedPubMedCentralGoogle Scholar
  28. da Silva Dias GA, Sousa RCM, Gomes LF, Caldas CAM, Nassiri R, Quaresma JAS, Fuzii HT (2016) Correlation between clinical symptoms and peripheral immune response in HAM/TSP. Microb Pathog 92:72–75CrossRefPubMedGoogle Scholar
  29. Dai L, Song J, Lu X, Deng YQ, Musyoki AM, Cheng H, Zhang Y, Yuan Y, Song H, Haywood J, Xiao H, Yan J, Shi Y, Qin CF, Qi J, Gao GF (2016) Structures of the Zika virus envelope protein and its complex with a Flavivirus broadly protective antibody. Cell Host Microbe 19(5):696–704CrossRefPubMedGoogle Scholar
  30. Dang J, Tiwari SK, Lichinchi G, Qin Y, Patil VS, Eroshkin AM, Rana TM (2016) Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 19(2):258–265CrossRefPubMedPubMedCentralGoogle Scholar
  31. Delvecchio R, Higa LM, Pezzuto P, Valadao AL, Garcez PP, Monteiro FL, et al. Chloroquine, an endocytosis blocking agent, inhibits Zika virus infection in different cell models. Iranian Journal of Basic Medical Sciences. 2016;8(12)Google Scholar
  32. Desrames A, Cassar O, Gout O, Hermine O, Taylor GP, Afonso PV, Gessain A (2014) Northern African strains of human T-lymphotropic virus type 1 arose from a recombination event. J Virol 88(17):9782–9788CrossRefPubMedPubMedCentralGoogle Scholar
  33. Di Paolo NC (2014) Recognition of human oncogenic viruses by host pattern-recognition receptors. Front Immunol 5:353CrossRefPubMedPubMedCentralGoogle Scholar
  34. Dickens BL, Yang J, Cook AR, Carrasco LR (2016) Time to empower release of insects carrying a dominant lethal and Wolbachia against Zika. Open Forum Infect Dis 3(2):ofw103CrossRefPubMedPubMedCentralGoogle Scholar
  35. Enose-Akahata Y, Vellucci A, Jacobson S (2017) Role of HTLV-1 tax and HBZ in the pathogenesis of HAM/TSP. Front Microbiol 8:2563CrossRefPubMedPubMedCentralGoogle Scholar
  36. Faye O, Freire CC, Iamarino A, Faye O, de Oliveira JV, Diallo M et al (2014) Molecular evolution of Zika virus during its emergence in the 20(th) century. PLoS Negl Trop Dis 8(1):e2636CrossRefPubMedPubMedCentralGoogle Scholar
  37. Fenizia C, Fiocchi M, Jones K, Parks RW, Ceribelli M, Chevalier SA, Edwards D, Ruscetti F, Pise-Masison CA, Franchini G (2014) Human T-cell leukemia/lymphoma virus type 1 p30, but not p12/p8, counteracts toll-like receptor 3 (TLR3) and TLR4 signaling in human monocytes and dendritic cells. J Virol 88(1):393–402CrossRefPubMedPubMedCentralGoogle Scholar
  38. Ferreira OC Jr, Planelles V, Rosenblatt JD (1997) Human T-cell leukemia viruses: epidemiology, biology, and pathogenesis. Blood Rev 11(2):91–104CrossRefPubMedGoogle Scholar
  39. Gallo RC, Willems L, Hasegawa H (2017) Screening transplant donors for HTLV-1 and -2. Blood 128(26):2–4Google Scholar
  40. Gessain A, Gallo RC, Franchini G (1992) Low degree of human T-cell leukemia/lymphoma virus type I genetic drift in vivo as a means of monitoring viral transmission and movement of ancient human populations. J Virol 66(4):2288–2295PubMedPubMedCentralGoogle Scholar
  41. Ginwala R, Caruso B, Khan ZK, Pattekar A, Chew GM, Corley MJ, Loonawat R, Jacobson S, Sreedhar S, Ndhlovu LC, Jain P (2017) HTLV-1 infection and neuropathogenesis in the context of Rag1-/-gammac-/- (RAG1-Hu) and BLT mice. J NeuroImmune Pharmacol 12(3):504–520CrossRefPubMedPubMedCentralGoogle Scholar
  42. Grant C, Oh U, Yao K, Yamano Y, Jacobson S (2008) Dysregulation of TGF-beta signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease. Blood 111(12):5601–5609CrossRefPubMedPubMedCentralGoogle Scholar
  43. Guerra M, Luna T, Souza A, Amorim C, Carvalho NB, Carvalho L, Tanajura D, Cardoso LS, Carvalho EM, Santos S (2018) Local and systemic production of proinflammatory chemokines in the pathogenesis of HAM/TSP. Cell Immunol 334:70–77CrossRefPubMedGoogle Scholar
  44. Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A, Luplertlop N, Perera-Lecoin M, Surasombatpattana P, Talignani L, Thomas F, Cao-Lormeau VM, Choumet V, Briant L, Desprès P, Amara A, Yssel H, Missé D (2015) Biology of Zika virus infection in human skin cells. J Virol 89(17):8880–8896CrossRefPubMedPubMedCentralGoogle Scholar
  45. Hanon E, Hall S, Taylor GP, Saito M, Davis R, Tanaka Y et al (2000) Abundant tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes. Blood 95(4):1386–1392PubMedGoogle Scholar
  46. Hasegawa A, Ohashi T, Hanabuchi S, Kato H, Takemura F, Masuda T, Kannagi M (2003) Expansion of human T-cell leukemia virus type 1 (HTLV-1) reservoir in orally infected rats: inverse correlation with HTLV-1-specific cellular immune response. J Virol 77(5):2956–2963CrossRefPubMedPubMedCentralGoogle Scholar
  47. Hishizawa M, Imada K, Kitawaki T, Ueda M, Kadowaki N, Uchiyama T (2004) Depletion and impaired interferon-alpha-producing capacity of blood plasmacytoid dendritic cells in human T-cell leukaemia virus type I-infected individuals. Br J Haematol 125(5):568–575CrossRefPubMedGoogle Scholar
  48. Jacobson S, Shida H, McFarlin DE, Fauci AS, Koenig S (1990) Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature 348(6298):245–248CrossRefPubMedGoogle Scholar
  49. Jain P, Manuel SL, Khan ZK, Ahuja J, Quann K, Wigdahl B (2009) DC-SIGN mediates cell-free infection and transmission of human T-cell lymphotropic virus type 1 by dendritic cells. J Virol 83(21):10908–10921CrossRefPubMedPubMedCentralGoogle Scholar
  50. Jain P, Lavorgna A, Sehgal M, Gao L, Ginwala R, Sagar D, Harhaj EW, Khan ZK (2015) Myocyte enhancer factor (MEF)-2 plays essential roles in T-cell transformation associated with HTLV-1 infection by stabilizing complex between Tax and CREB. Retrovirology 12:23CrossRefPubMedPubMedCentralGoogle Scholar
  51. Jain R, Coloma J, Garcia-Sastre A, Aggarwal AK (2016) Structure of the NS3 helicase from Zika virus. Journal of Neuroinfectious Diseases 23(8):752–754Google Scholar
  52. Jaworski E, Narayanan A, Van Duyne R, Shabbeer-Meyering S, Iordanskiy S, Saifuddin M et al (2014) Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain tax protein. J Biol Chem 289(32):22284–22305CrossRefPubMedPubMedCentralGoogle Scholar
  53. Johnson JM, Nicot C, Fullen J, Ciminale V, Casareto L, Mulloy JC, Jacobson S, Franchini G (2001) Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia/lymphotropic virus type 1 p12(I) protein. J Virol 75(13):6086–6094CrossRefPubMedPubMedCentralGoogle Scholar
  54. Journo C, Mahieux R (2011) HTLV-1 and innate immunity. Viruses 3(8):1374–1394CrossRefPubMedPubMedCentralGoogle Scholar
  55. Jurado KA, Simoni MK, Tang Z, Uraki R, Hwang J, Householder S, et al. Zika virus productively infects primary human placenta-specific macrophages. JCI Insight. 2016;1(13)Google Scholar
  56. Kalume F, Lee SM, Morcos Y, Callaway JC, Levin MC (2004) Molecular mimicry: cross-reactive antibodies from patients with immune-mediated neurologic disease inhibit neuronal firing. J Neurosci Res 77(1):82–89CrossRefPubMedGoogle Scholar
  57. Kannagi M, Hasegawa A, Takamori A, Kinpara S, Utsunomiya A (2012) The roles of acquired and innate immunity in human T-cell leukemia virus type 1-mediated diseases. Front Microbiol 3:323CrossRefPubMedPubMedCentralGoogle Scholar
  58. Kinoshita K, Amagasaki T, Hino S, Doi H, Yamanouchi K, Ban N, Momita S, Ikeda S, Kamihira S, Ichimaru M (1987) Milk-borne transmission of HTLV-I from carrier mothers to their children. Jpn J Cancer Res 78(7):674–680PubMedGoogle Scholar
  59. Kramer A, Maloney EM, Morgan OS, Rodgers-Johnson P, Manns A, Murphy EL et al (1995) Risk factors and cofactors for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica. Emerging Microbes and Infections 142(11):1212–1220Google Scholar
  60. Kress AK, Grassmann R, Fleckenstein B (2011) Cell surface markers in HTLV-1 pathogenesis. Viruses 3(8):1439–1459CrossRefPubMedPubMedCentralGoogle Scholar
  61. Kumar A, Hou S, Airo AM, Limonta D, Mancinelli V, Branton W, Power C, Hobman TC (2016) Zika virus inhibits type-I interferon production and downstream signaling. EMBO Rep 17(12):1766–1775CrossRefPubMedPubMedCentralGoogle Scholar
  62. Kuno G, Chang GJ (2007) Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch Virol 152(4):687–696CrossRefPubMedGoogle Scholar
  63. Lathia JD, Okun E, Tang SC, Griffioen K, Cheng A, Mughal MR, Laryea G, Selvaraj PK, ffrench-Constant C, Magnus T, Arumugam TV, Mattson MP (2008) Toll-like receptor 3 is a negative regulator of embryonic neural progenitor cell proliferation. J Neurosci 28(51):13978–13984CrossRefPubMedPubMedCentralGoogle Scholar
  64. Lepoutre V, Jain P, Quann K, Wigdahl B, Khan ZK (2009) Role of resident CNS cell populations in HTLV-1-associated neuroinflammatory disease. Front Biosci 14:1152–1168CrossRefPubMedCentralGoogle Scholar
  65. Levin MC, Lee SM, Kalume F, Morcos Y, Dohan FC Jr, Hasty KA et al (2002) Autoimmunity due to molecular mimicry as a cause of neurological disease. Nat Med 8(5):509–513CrossRefPubMedPubMedCentralGoogle Scholar
  66. Li H, Saucedo-Cuevas L, Regla-Nava JA, Chai G, Sheets N, Tang W, Terskikh AV, Shresta S, Gleeson JG (2016) Zika virus infects neural progenitors in the adult mouse brain and alters proliferation. Cell Stem Cell 19(5):593–598CrossRefPubMedPubMedCentralGoogle Scholar
  67. Lima NS, Rolland M, Modjarrad K, Trautmann L (2017) T cell immunity and Zika virus vaccine development. Trends Immunol 38(8):594–605CrossRefPubMedGoogle Scholar
  68. Liu B, Woltman AM, Janssen HL, Boonstra A (2009) Modulation of dendritic cell function by persistent viruses. Am J Trop Med Hyg 85(2):205–214Google Scholar
  69. Ma G, Yasunaga J, Matsuoka M (2016) Multifaceted functions and roles of HBZ in HTLV-1 pathogenesis. Retrovirology 13:16CrossRefPubMedPubMedCentralGoogle Scholar
  70. Magri MC, Brigido LF, Rodrigues R, Morimoto HK, Ferreira JL, Caterino-de-Araujo A (2012) Phylogenetic and similarity analysis of HTLV-1 isolates from HIV-coinfected patients from the south and southeast regions of Brazil. AIDS Res Hum Retrovir 28(1):110–114CrossRefPubMedGoogle Scholar
  71. Maharajan MK, Ranjan A, Chu JF, Foo WL, Chai ZX, Lau EY et al (2016) Zika virus infection: current concerns and perspectives. Clin Rev Allergy Immunol 51(3):383–394CrossRefPubMedGoogle Scholar
  72. Mahgoub M, Yasunaga JI, Iwami S, Nakaoka S, Koizumi Y, Shimura K, Matsuoka M (2018) 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 U S A 115(6):E1269–E1E78CrossRefPubMedPubMedCentralGoogle Scholar
  73. Mahieux R, Gessain A (2009) The human HTLV-3 and HTLV-4 retroviruses: new members of the HTLV family. Pathol Biol 57(2):161–166CrossRefPubMedGoogle Scholar
  74. Makhluf H, Shresta S. Development of Zika virus vaccines. Vaccines (Basel). 2018;6(1)Google Scholar
  75. Maloney EM, Cleghorn FR, Morgan OS, Rodgers-Johnson P, Cranston B, Jack N et al (1998) Incidence of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad. J Acquir Immune Defic Syndr Hum Retrovirol 17(2):167–170CrossRefPubMedGoogle Scholar
  76. Manuel SL, Schell TD, Acheampong E, Rahman S, Khan ZK, Jain P (2009) Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease. J Leukoc Biol 86(5):1205–1216CrossRefPubMedPubMedCentralGoogle Scholar
  77. Manuel SL, Sehgal M, Connolly J, Makedonas G, Khan ZK, Gardner J, Betts MR, Jain P (2013) Lack of recall response to tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1. J Clin Immunol 33(7):1223–1239CrossRefPubMedPubMedCentralGoogle Scholar
  78. Martins ML, de Freitas Carneiro-Proietti AB, Nicolato R, de Miranda DM, Romanelli LCF (2018) HTLV-1 proviral load in cerebrospinal fluid may not be a good marker to differentiate asymptomatic carriers with high proviral load in blood from HAM/TSP patients. J Neuro-Oncol 24(4):432–438Google Scholar
  79. Matsuoka M, Green PL (2009) The HBZ gene, a key player in HTLV-1 pathogenesis. Retrovirology 6:71CrossRefPubMedPubMedCentralGoogle Scholar
  80. McArthur MA. Zika virus: recent advances towards the development of vaccines and therapeutics. Viruses. 2017;9(6)Google Scholar
  81. Mead PS, Hills SL, Brooks JT (2018) Zika virus as a sexually transmitted pathogen. Curr Opin Infect Dis 31(1):39–44CrossRefPubMedGoogle Scholar
  82. Merfeld E, Ben-Avi L, Kennon M, Cerveny KL. Potential mechanisms of Zika-linked microcephaly. Wiley Interdiscip Rev Dev Biol 2017;6(4)Google Scholar
  83. Miner JJ, Diamond MS (2017) Zika virus pathogenesis and tissue tropism. Cell Host Microbe 21(2):134–142CrossRefPubMedPubMedCentralGoogle Scholar
  84. Miner JJ, Cao B, Govero J, Smith AM, Fernandez E, Cabrera OH, Garber C, Noll M, Klein RS, Noguchi KK, Mysorekar IU, Diamond MS (2016) Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell Discovery 165(5):1081–1091Google Scholar
  85. Montanheiro PA, Penalva de Oliveira AC, Smid J, Fukumori LM, Olah I, da S Duarte AJ et al (2009) The elevated interferon gamma production is an important immunological marker in HAM/TSP pathogenesis. Scand J Immunol 70(4):403–407CrossRefPubMedGoogle Scholar
  86. Murphy EL, Lee TH, Chafets D, Nass CC, Wang B, Loughlin K, Smith D, HTLV Outcomes Study Investigators (2004) Higher human T lymphotropic virus (HTLV) provirus load is associated with HTLV-I versus HTLV-II, with HTLV-II subtype A versus B, and with male sex and a history of blood transfusion. J Infect Dis 190(3):504–510CrossRefPubMedGoogle Scholar
  87. Norris PJ, Hirschkorn DF, DeVita DA, Lee TH, Murphy EL (2010) Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells. Virulence 1(1):19–28CrossRefPubMedPubMedCentralGoogle Scholar
  88. Oliere S, Hernandez E, Lezin A, Arguello M, Douville R, Nguyen TL et al (2010) HTLV-1 evades type I interferon antiviral signaling by inducing the suppressor of cytokine signaling 1 (SOCS1). PLoS Pathog 6(11):e1001177CrossRefPubMedPubMedCentralGoogle Scholar
  89. Olindo S, Jeannin S, Saint-Vil M, Signate A, Edimonana-Kaptue M, Joux J, Merle H, Richard P, Granjeaud S, Cabre P, Smadja D, Cesaire R, Lezin A (2018) Temporal trends in Human T-Lymphotropic virus 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) incidence in Martinique over 25 years (1986-2010). PLoS Negl Trop Dis 12(3):e0006304CrossRefPubMedPubMedCentralGoogle Scholar
  90. Ornelas AM, Pezzuto P, Silveira PP, Melo FO, Ferreira TA, Oliveira-Szejnfeld PS et al (2017) Immune activation in amniotic fluid from Zika virus-associated microcephaly. Ann Neurol 81(1):152–156CrossRefPubMedGoogle Scholar
  91. Paiva A, Casseb J (2014) Sexual transmission of human T-cell lymphotropic virus type 1. Rev Soc Bras Med Trop 47(3):265–274CrossRefPubMedGoogle Scholar
  92. Paiva A, Smid J, Haziot MEJ, Assone T, Pinheiro S, Fonseca LAM, de Oliveira ACP, Casseb J (2017) High risk of heterosexual transmission of human T-cell lymphotropic virus type 1 infection in Brazil. J Med Virol 89(7):1287–1294CrossRefPubMedGoogle Scholar
  93. Paiva AM, Assone T, Haziot MEJ, Smid J, Fonseca LAM, Luiz ODC et al (2018) Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring. Sci Rep 8(1):7742CrossRefPubMedPubMedCentralGoogle Scholar
  94. Parker CE, Daenke S, Nightingale S, Bangham CR (1992) Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis. Iran J Immunol 188(2):628–636Google Scholar
  95. Parra B, Lizarazo J, Jimenez-Arango JA, Zea-Vera AF, Gonzalez-Manrique G, Vargas J et al (2016) Guillain-Barre syndrome associated with Zika virus infection in Colombia. N Engl J Med 375(16):1513–1523CrossRefPubMedGoogle Scholar
  96. Peloponese JM Jr, Jeang KT (2006) Role for Akt/protein kinase B and activator protein-1 in cellular proliferation induced by the human T-cell leukemia virus type 1 tax oncoprotein. J Biol Chem 281(13):8927–8938CrossRefPubMedGoogle Scholar
  97. Petersen LR, Jamieson DJ, Powers AM, Honein MA (2016) Zika virus. N Engl J Med 374(16):1552–1563CrossRefPubMedGoogle Scholar
  98. Philip S, Zahoor MA, Zhi H, Ho YK, Giam CZ (2014) Regulation of human T-lymphotropic virus type I latency and reactivation by HBZ and Rex. PLoS Pathog 10(4):e1004040CrossRefPubMedPubMedCentralGoogle Scholar
  99. Pise-Masison CA, de Castro-Amarante MF, Enose-Akahata Y, Buchmann RC, Fenizia C, Washington Parks R, Edwards D, Fiocchi M, Alcantara LC, Bialuk I, Graham J, Walser JC, McKinnon K, Galvão-Castro B, Gessain A, Venzon D, Jacobson S, Franchini G (2014) Co-dependence of HTLV-1 p12 and p8 functions in virus persistence. PLoS Pathog 10(11):e1004454CrossRefPubMedPubMedCentralGoogle Scholar
  100. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980) Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A 77(12):7415–7419CrossRefPubMedPubMedCentralGoogle Scholar
  101. Poland GA, Kennedy RB, Ovsyannikova IG, Palacios R, Ho PL, Kalil J. Development of vaccines against Zika virus. Lancet Infect Dis. 2018Google Scholar
  102. Quaresma JAS, Yoshikawa GT, Koyama RVL, Dias GAS, Fujihara S, Fuzii HT (2015) HTLV-1, immune response and autoimmunity. Viruses 8(1):2–11CrossRefGoogle Scholar
  103. Quicke KM, Bowen JR, Johnson EL, McDonald CE, Ma H, O'Neal JT et al (2016) Zika virus infects human placental macrophages. Cell Host Microbe 20(1):83–90CrossRefPubMedPubMedCentralGoogle Scholar
  104. Rafatpanah H, Pravica V, Faridhosseini R, Tabatabaei A, Ollier W, Poulton K et al (2007) Association between HLA-DRB1*01 and HLA-Cw*08 and outcome following HTLV-I infection. Iran J Immunol 4(2):94–100PubMedGoogle Scholar
  105. Rafatpanah H, Farid Hosseini R, Pourseyed SH (2013) The impact of immune response on HTLV-I in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Iran J Basic Med Sci 16(3):235–241PubMedPubMedCentralGoogle Scholar
  106. Rahman S, Quann K, Pandya D, Singh S, Khan ZK, Jain P (2012) HTLV-1 Tax mediated downregulation of miRNAs associated with chromatin remodeling factors in T cells with stably integrated viral promoter. PLoS One 7(4):e34490CrossRefPubMedPubMedCentralGoogle Scholar
  107. Ramaiah A, Dai L, Contreras D, Sinha S, Sun R, Arumugaswami V (2017) Comparative analysis of protein evolution in the genome of pre-epidemic and epidemic Zika virus. Infect Genet Evol 51:74–85CrossRefPubMedGoogle Scholar
  108. Ratner L, Philpott T, Trowbridge DB (1991) Nucleotide sequence analysis of isolates of human T-lymphotropic virus type 1 of diverse geographical origins. AIDS Res Hum Retrovir 7(11):923–941CrossRefPubMedGoogle Scholar
  109. Retallack H, Di Lullo E, Arias C, Knopp KA, Laurie MT, Sandoval-Espinosa C et al (2016) Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci U S A 113(50):14408–14413CrossRefPubMedPubMedCentralGoogle Scholar
  110. Ribeiro MA, Martins ML, Teixeira C, Ladeira R, Oliveira Mde F, Januario JN et al (2012) Blocking vertical transmission of human T cell lymphotropic virus type 1 and 2 through breastfeeding interruption. Pediatr Infect Dis J 31(11):1139–1143CrossRefPubMedGoogle Scholar
  111. Routhu NK, Byrareddy SN (2017) Host-virus interaction of ZIKA virus in modulating disease pathogenesis. J NeuroImmune Pharmacol 12(2):219–232CrossRefPubMedPubMedCentralGoogle Scholar
  112. Sagar D, Masih S, Schell T, Jacobson S, Comber JD, Philip R, Wigdahl B, Jain P, Khan ZK (2014) In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine. Vaccine 32(26):3274–3284CrossRefPubMedPubMedCentralGoogle Scholar
  113. Saito M, Jain P, Tsukasaki K, Bangham CR (2012) HTLV-1 infection and its associated diseases. Leuk Res Treatment 2012:123637PubMedPubMedCentralGoogle Scholar
  114. 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(3):720–725CrossRefPubMedPubMedCentralGoogle Scholar
  115. Saw WG, Pan A, Subramanian Manimekalai MS, Gruber G (2017) Structural features of Zika virus non-structural proteins 3 and -5 and its individual domains in solution as well as insights into NS3 inhibition. Antivir Res 141:73–90CrossRefPubMedGoogle Scholar
  116. Schlub TE, Grimm AJ, Smyth RP, Cromer D, Chopra A, Mallal S, Venturi V, Waugh C, Mak J, Davenport MP (2014) Fifteen to twenty percent of HIV substitution mutations are associated with recombination. J Virol 88(7):3837–3849CrossRefPubMedPubMedCentralGoogle Scholar
  117. Schütze M, Romanelli LCF, Rosa DV, Carneiro-Proietti ABF, Nicolato R, Romano-Silva MA, et al. Brain metabolism changes in patients infected with HTLV-1. Frontiers in Molecular Neuroscience. 2017;10(52)Google Scholar
  118. Shankar A, Patil AA, Skariyachan S (2017) Recent perspectives on genome, transmission, clinical manifestation, diagnosis, therapeutic strategies, vaccine developments, and challenges of Zika virus research. Front Microbiol 8:1761CrossRefPubMedPubMedCentralGoogle Scholar
  119. Shuh M, Beilke M (2005) The human T-cell leukemia virus type 1 (HTLV-1): new insights into the clinical aspects and molecular pathogenesis of adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM). Microsc Res Tech 68(3–4):176–196CrossRefPubMedGoogle Scholar
  120. Siekevitz M, Feinberg MB, Holbrook N, Wong-Staal F, Greene WC (1987) Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. Proc Natl Acad Sci U S A 84(15):5389–5393CrossRefPubMedPubMedCentralGoogle Scholar
  121. Simoni MK, Jurado KA, Abrahams VM, Fikrig E, Guller S. Zika virus infection of Hofbauer cells. Am J Reprod Immunol. 2017;77(2)Google Scholar
  122. Sirohi D, Kuhn RJ (2017) Zika virus structure, maturation, and receptors. J Infect Dis 216(suppl_10):S935–SS44CrossRefPubMedPubMedCentralGoogle Scholar
  123. Slater CMSA, Ribeiro LCP, Puccioni-Sohler M (2012) Difficulties in HAM/TSP diagnosis. Arq Neuropsiquiatr 70(9):686–690CrossRefPubMedGoogle Scholar
  124. Solomon IH, Milner DA, Folkerth RD. Neuropathology of Zika virus infection. J Neuroinfect Dis. 2016;7(2)Google Scholar
  125. Song BH, Yun SI, Woolley M, Lee YM (2017) Zika virus: history, epidemiology, transmission, and clinical presentation. J Neuroimmunol 308:50–64CrossRefPubMedGoogle Scholar
  126. Stettler K, Beltramello M, Espinosa DA, Graham V, Cassotta A, Bianchi S, Vanzetta F, Minola A, Jaconi S, Mele F, Foglierini M, Pedotti M, Simonelli L, Dowall S, Atkinson B, Percivalle E, Simmons CP, Varani L, Blum J, Baldanti F, Cameroni E, Hewson R, Harris E, Lanzavecchia A, Sallusto F, Corti D (2016) Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection. Science 353(6301):823–826CrossRefPubMedGoogle Scholar
  127. Sugata K, Satou Y, Yasunaga J, Hara H, Ohshima K, Utsunomiya A, Mitsuyama M, Matsuoka M (2012) HTLV-1 bZIP factor impairs cell-mediated immunity by suppressing production of Th1 cytokines. Blood 119(2):434–444CrossRefPubMedPubMedCentralGoogle Scholar
  128. Takahashi K, Takezaki T, Oki T, Kawakami K, Yashiki S, Fujiyoshi T, Usuku K, The Mother-to-Child Transmission Study Group, Mueller N, Osame M, Miyata K, Nagata Y, Sonoda S (1991) Inhibitory effect of maternal antibody on mother-to-child transmission of human T-lymphotropic virus type I. The Mother-to-Child Transmission Study Group. Int J Cancer 49(5):673–677CrossRefPubMedGoogle Scholar
  129. Takeoka H, Furusyo N, Toyoda K, Murata M, Sagara Y, Kashiwagi S et al (2007) Antibody to the human T-lymphotropic virus type 1 (HTLV-1) envelope protein Gp46 in patients co-infected with HCV and HTLV-1. Am J Trop Med Hyg 77(1):192–196CrossRefPubMedGoogle Scholar
  130. Trevino A, Alcantara LC Jr, Benito R, Caballero E, Aguilera A, Ramos JM et al (2014) Molecular epidemiology and clinical features of human T cell lymphotropic virus type 1 infection in Spain. AIDS Res Hum Retrovir 30(9):856–862CrossRefPubMedGoogle Scholar
  131. Van Tienen C, Jakobsen M, Van Der Loeff MS (2012) Stopping breastfeeding to prevent vertical transmission of HTLV-1 in resource-poor settings: beneficial or harmful? Arch Gynecol Obstet 286(1):255–256CrossRefPubMedPubMedCentralGoogle Scholar
  132. Wang L, Valderramos SG, Wu A, Ouyang S, Li C, Brasil P, Bonaldo M, Coates T, Nielsen-Saines K, Jiang T, Aliyari R, Cheng G (2016) From mosquitos to humans: genetic evolution of Zika virus. Cell Host Microbe 19(5):561–565CrossRefPubMedPubMedCentralGoogle Scholar
  133. Wang A, Thurmond S, Islas L, Hui K, Hai R (2017) Zika virus genome biology and molecular pathogenesis. Emerg Microbes Infect 6(3):e13PubMedPubMedCentralGoogle Scholar
  134. Wang J, Liu J, Zhou R, Ding X, Zhang Q, Zhang C, et al. Zika virus infected primary microglia impairs NPCs proliferation and differentiation. Biochem Biophys Res Commun. 2018Google Scholar
  135. Wen Z, Song H, Ming GL (2017) How does Zika virus cause microcephaly? Genes Dev 31(9):849–861CrossRefPubMedPubMedCentralGoogle Scholar
  136. Willems L, Hasegawa H, Accolla R, Bangham C, Bazarbachi A, Bertazzoni U, Carneiro-Proietti ABF, Cheng H, Chieco-Bianchi L, Ciminale V, Coelho-dos-Reis J, Esparza J, Gallo RC, Gessain A, Gotuzzo E, Hall W, Harford J, Hermine O, Jacobson S, Macchi B, Macpherson C, Mahieux R, Matsuoka M, Murphy E, Peloponese JM, Simon V, Tagaya Y, Taylor GP, Watanabe T, Yamano Y (2017) Reducing the global burden of HTLV-1 infection: an agenda for research and action. Antivir Res 137:41–48CrossRefPubMedGoogle Scholar
  137. Wu Y, Liu Q, Zhou J, Xie W, Chen C, Wang Z, Yang H, Cui J (2017) Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro. Cell Discov 3:17006CrossRefPubMedPubMedCentralGoogle Scholar
  138. Yakob L, Walker T (2016) Zika virus outbreak in the Americas: the need for novel mosquito control methods. Leukemia Research and Treatment 4(3):e148–e149Google Scholar
  139. Yamano Y, Sato T (2012) Clinical pathophysiology of human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis. Leukemia Research and Treatment 3:389Google Scholar
  140. Yamano Y, Kitze B, Yashiki S, Usuku K, Fujiyoshi T, Kaminagayoshi T, Unoki K, Izumo S, Osame M, Sonoda S (1997) Preferential recognition of synthetic peptides from HTLV-I gp21 envelope protein by HLA-DRB1 alleles associated with HAM/TSP (HTLV-I-associated myelopathy/tropical spastic paraparesis). J Neuroimmunol 76(1–2):50–60CrossRefPubMedGoogle Scholar
  141. Younger DS (2016) Epidemiology of Zika virus. Neurol Clin 34(4):1049–1056CrossRefPubMedGoogle Scholar
  142. Yu F, Itoyama Y, Fujihara K, Goto I (1991) Natural killer (NK) cells in HTLV-I-associated myelopathy/tropical spastic paraparesis-decrease in NK cell subset populations and activity in HTLV-I seropositive individuals. J Neuroimmunol 33(2):121–128CrossRefPubMedGoogle Scholar
  143. Yuen CK, Chan CP, Fung SY, Wang PH, Wong WM, Tang HV et al (2016) Suppression of type I interferon production by human T-cell leukemia virus type 1 oncoprotein tax through inhibition of IRF3 phosphorylation. Open Forum Infectious Disease 90(8):3902–3912Google Scholar
  144. Zhao T (2016) The role of HBZ in HTLV-1-induced oncogenesis. Viruses 8(2):1–12CrossRefGoogle Scholar
  145. Zhao T, Satou Y, Sugata K, Miyazato P, Green PL, Imamura T, Matsuoka M (2011) HTLV-1 bZIP factor enhances TGF-beta signaling through p300 coactivator. Pathogens and Global Health 118(7):1865–1876Google Scholar
  146. Zhao B, Yi G, Du F, Chuang YC, Vaughan RC, Sankaran B et al (2017) Structure and function of the Zika virus full-length NS5 protein. Nat Commun 8:14762CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  1. 1.Department of Microbiology and Immunology, and the Institute for Molecular Medicine and Infectious DiseaseDrexel University College of MedicinePhiladelphiaUSA
  2. 2.PA College of Optometry at Salus UniversityElkins ParkUSA

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