Review Article | Published:

The emergence of Zika virus and its new clinical syndromes

Naturevolume 560pages573581 (2018) | Download Citation

Abstract

Zika virus (ZIKV) is a mosquito-transmitted flavivirus that has emerged as a global health threat because of its potential to generate explosive epidemics and ability to cause congenital disease in the context of infection during pregnancy. Whereas much is known about the biology of related flaviviruses, the unique features of ZIKV pathogenesis, including infection of the fetus, persistence in immune-privileged sites and sexual transmission, have presented new challenges. The rapid development of cell culture and animal models has facilitated a new appreciation of ZIKV biology. This knowledge has created opportunities for the development of countermeasures, including multiple ZIKV vaccine candidates, which are advancing through clinical trials. Here we describe the recent advances that have led to a new understanding of the causes and consequences of the ZIKV epidemic.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.

    Weaver, S. C. et al. Zika virus: history, emergence, biology, and prospects for control. Antiviral Res. 130, 69–80 (2016).

  2. 2.

    Duffy, M. R. et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N. Engl. J. Med. 360, 2536–2543 (2009).

  3. 3.

    Musso, D. et al. Zika virus in French Polynesia 2013–14: anatomy of a completed outbreak. Lancet Infect. Dis. 18, e172–e182 (2018).

  4. 4.

    Metsky, H. C. et al. Zika virus evolution and spread in the Americas. Nature 546, 411–415 (2017).

  5. 5.

    Netto, E. M. et al. High Zika virus seroprevalence in Salvador, northeastern Brazil limits the potential for further outbreaks. MBio 8, e01390-17 (2017).

  6. 6.

    Annamalai, A. S. et al. Zika virus encoding non-glycosylated envelope protein is attenuated and defective in neuroinvasion. J. Virol. e01348-17 (2017).

  7. 7.

    Barba-Spaeth, G. et al. Structural basis of potent Zika–dengue virus antibody cross-neutralization. Nature 536, 48–53 (2016).

  8. 8.

    Fernandez, E. et al. Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection. Nat. Immunol. 18, 1261–1269 (2017).

  9. 9.

    Culshaw, A., Mongkolsapaya, J. & Screaton, G. R. The immunopathology of dengue and Zika virus infections. Curr. Opin. Immunol. 48, 1–6 (2017).

  10. 10.

    Faria, N. R. et al. Zika virus in the Americas: early epidemiological and genetic findings. Science 352, 345–349 (2016). Key phylogenetic analysis of ZIKV entry into the Americas.

  11. 11.

    Prasad, V. M. et al. Structure of the immature Zika virus at 9 Å resolution. Nat. Struct. Mol. Biol. 24, 184–186 (2017).

  12. 12.

    Kostyuchenko, V. A. et al. Structure of the thermally stable Zika virus. Nature 533, 425–428 (2016).

  13. 13.

    Sirohi, D. et al. The 3.8 Å resolution cryo-EM structure of Zika virus. Science 352, 467–470 (2016). Two papers 12 , 13 provide high-resolution cryo-EM structures of ZIKV.

  14. 14.

    Rey, F. A., Stiasny, K. & Heinz, F. X. Flavivirus structural heterogeneity: implications for cell entry. Curr. Opin. Virol. 24, 132–139 (2017

  15. 15.

    Aubry, M. et al. Zika virus seroprevalence, French Polynesia, 2014–2015. Emerg. Infect. Dis. 23, 669–672 (2017).

  16. 16.

    Swaminathan, S., Schlaberg, R., Lewis, J., Hanson, K. E. & Couturier, M. R. Fatal Zika virus infection with secondary nonsexual transmission. N. Engl. J. Med. 375, 1907–1909 (2016).

  17. 17.

    Carteaux, G. et al. Zika virus associated with meningoencephalitis. N. Engl. J. Med. 374, 1595–1596 (2016).

  18. 18.

    Karimi, O. et al. Thrombocytopenia and subcutaneous bleedings in a patient with Zika virus infection. Lancet 387, 939–940 (2016).

  19. 19.

    Dirlikov, E. et al. Postmortem findings in patient with Guillain–Barré syndrome and Zika virus infection. Emerg. Infect. Dis. 24, 114–117 (2018).

  20. 20.

    Styczynski, A. R. et al. Increased rates of Guillain–Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil. PLoS Negl. Trop. Dis. 11, e0005869 (2017).

  21. 21.

    Murray, K. O. et al. Prolonged detection of Zika virus in vaginal secretions and whole blood. Emerg. Infect. Dis. 23, 99–101 (2017).

  22. 22.

    Mansuy, J. M. et al. Zika Virus infection and prolonged viremia in whole-blood specimens. Emerg. Infect. Dis. 23, 863–865 (2017).

  23. 23.

    Michlmayr, D., Andrade, P., Gonzalez, K., Balmaseda, A. & Harris, E. CD14+CD16+ monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua. Nat. Microbiol. 2, 1462–1470 (2017).

  24. 24.

    Miner, J. J. et al. Zika virus infection in mice causes panuveitis with shedding of virus in tears. Cell Rep. 16, 3208–3218 (2016).

  25. 25.

    Kodati, S. et al. Bilateral posterior uveitis associated with Zika virus infection. Lancet 389, 125–126 (2017).

  26. 26.

    Parke, D. W., III et al. Serologically confirmed Zika-related unilateral acute maculopathy in an adult. Ophthalmology 123, 2432–2433 (2016).

  27. 27.

    Tan, J. J. L. et al. Persistence of Zika virus in conjunctival fluid of convalescence patients. Sci. Rep. 7, 11194 (2017).

  28. 28.

    Mansuy, J. M. et al. Zika virus in semen and spermatozoa. Lancet Infect. Dis. 16, 1106–1107 (2016).

  29. 29.

    Mead, P. S. et al. Zika virus shedding in semen of symptomatic infected men. N. Engl. J. Med. 378, 1377–1385 (2018).

  30. 30.

    Hirsch, A. J. et al. Zika virus infection of rhesus macaques leads to viral persistence in multiple tissues. PLoS Pathog. 13, e1006219 (2017).

  31. 31.

    Govero, J. et al. Zika virus infection damages the testes in mice. Nature 540, 438–442 (2016).

  32. 32.

    Ma, W. et al. Zika virus causes testis damage and leads to male infertility in mice. Cell 167, 1511–1524 (2016).

  33. 33.

    Joguet, G. et al. Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study. Lancet Infect. Dis. 17, 1200–1208 (2017).

  34. 34.

    Russell, K. et al. Male-to-female sexual transmission of Zika virus—United States, January–April 2016. Clin. Infect. Dis. 64, 211–213 (2017).

  35. 35.

    Deckard, D. T. et al. Male-to-male sexual transmission of Zika virus—Texas, January 2016. MMWR Morb. Mortal. Wkly Rep. 65, 372–374 (2016).

  36. 36.

    Oehler, E. et al. Zika virus infection complicated by Guillain–Barré syndrome—case report, French Polynesia, December 2013. Euro Surveill. 19, 20720 (2014).

  37. 37.

    Parra, B. et al. Guillain–Barré syndrome associated with Zika virus infection in Colombia. N. Engl. J. Med. 375, 1513–1523 (2016).

  38. 38.

    dos Santos, T. et al. Zika virus and the Guillain–Barré Syndrome — case series from seven countries. N. Engl. J. Med. 375, 1598–1601 (2016). Description of ZIKV-associated Guillain–Barré Syndrome in the Americas.

  39. 39.

    Dirlikov, E. et al. Acute Zika virus infection as a risk factor for Guillain–Barré syndrome in Puerto Rico. J. Am. Med. Assoc. 318, 1498–1500 (2017).

  40. 40.

    Arora, N., Sadovsky, Y., Dermody, T. S. & Coyne, C. B. Microbial vertical transmission during human pregnancy. Cell Host Microbe 21, 561–567 (2017).

  41. 41.

    Miner, J. J. et al. Zika virus infection during pregnancy in mice causes placental damage and fetal demise. Cell 165, 1081–1091 (2016). Establishment of a mouse model of the fetal injury caused by ZIKV.

  42. 42.

    Sheridan, M. A. et al. Vulnerability of primitive human placental trophoblast to Zika virus. Proc. Natl Acad. Sci. USA 114, E1587–E1596 (2017).

  43. 43.

    Bayer, A. et al. Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe 19, 705–712 (2016).

  44. 44.

    Jagger, B. W. et al. Gestational Stage and IFN-λ signaling regulate ZIKV infection in utero. Cell Host Microbe 22, 366–376 (2017).

  45. 45.

    Quicke, K. M. et al. Zika virus infects human placental macrophages. Cell Host Microbe 20, 83–90 (2016).

  46. 46.

    Richard, A. S. et al. AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses. Proc. Natl Acad. Sci. USA 114, 2024–2029 (2017).

  47. 47.

    Martines, R. B. et al. Pathology of congenital Zika syndrome in Brazil: a case series. Lancet 388, 898–904 (2016).

  48. 48.

    Platt, D. J. et al. Zika virus-related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice. Sci. Transl. Med. 10, eaao7090 (2018).

  49. 49.

    Delaney, A. et al. Population-Based surveillance of birth defects potentially related to Zika virus infection — 15 States and U.S. Territories, 2016. MMWR Morb. Mortal. Wkly Rep. 67, 91–96 (2018).

  50. 50.

    Li, H., Saucedo-Cuevas, L., Shresta, S. & Gleeson, J. G. The neurobiology of Zika virus. Neuron 92, 949–958 (2016).

  51. 51.

    Tang, H. et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 18, 587–590 (2016). Key paper describing ZIKV infection and injury of neuroprogenitor cells.

  52. 52.

    Lum, F. M. et al. Zika virus infects human fetal brain microglia and induces inflammation. Clin. Infect. Dis. 64, 914–920 (2017).

  53. 53.

    Meertens, L. et al. Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses. Cell Rep. 18, 324–333 (2017).

  54. 54.

    Retallack, H. et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc. Natl Acad. Sci. USA 113, 14408–14413 (2016).

  55. 55.

    Brasil, P. et al. Zika virus infection in pregnant women in Rio de Janeiro. N. Engl. J. Med. 375, 2321–2334 (2016). Study describing the effects of ZIKV during pregnancy in Brazil.

  56. 56.

    Cauchemez, S. et al. Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study. Lancet 387, 2125–2132 (2016).

  57. 57.

    Shapiro-Mendoza, C. K. et al. Pregnancy outcomes after maternal Zika virus infection during pregnancy — U.S. Territories, January 1, 2016–April 25, 2017. MMWR Morb. Mortal. Wkly Rep. 66, 615–621 (2017).

  58. 58.

    Moura da Silva, A. A. et al. Early growth and neurologic outcomes of infants with probable congenital Zika virus syndrome. Emerg. Infect. Dis. 22, 1953–1956 (2016).

  59. 59.

    Satterfield-Nash, A. et al. Health and development at age 19–24 months of 19 children who were born with microcephaly and laboratory evidence of congenital Zika virus infection during the 2015 Zika virus outbreak — Brazil, 2017. MMWR Morb. Mortal. Wkly Rep. 66, 1347–1351 (2017).

  60. 60.

    Lazear, H. M. et al. A mouse model of Zika virus pathogenesis. Cell Host Microbe 19, 720–730 (2016).

  61. 61.

    Honein, M. A. et al. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. J. Am. Med. Assoc. 317, 59–68 (2017).

  62. 62.

    Cugola, F. R. et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature 534, 267–271 (2016). Establishment of a mouse model of fetal injury and microcephaly caused by ZIKV infection.

  63. 63.

    Xavier-Neto, J. et al. Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: a developmental study. PLoS Negl. Trop. Dis. 11, e0005363 (2017).

  64. 64.

    Vermillion, M. S. et al. Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes. Nat. Commun. 8, 14575 (2017).

  65. 65.

    Szaba, F. M. et al. Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection. PLoS Pathog. 14, e1006994 (2018).

  66. 66.

    Li, C. et al. Zika virus disrupts neural progenitor development and leads to microcephaly in mice. Cell Stem Cell 19, 120–126 (2016).

  67. 67.

    Yockey, L. J. et al. Vaginal exposure to Zika virus during pregnancy leads to fetal brain infection. Cell 166, 1247–1256 (2016). Animal study showing that intravaginal transmission of ZIKV can result in fetal brain injury.

  68. 68.

    Gorman, M. J. et al. An immunocompetent mouse model of Zika virus infection. Cell Host Microbe 23, 672–685 (2018).

  69. 69.

    Dudley, D. M. et al. A rhesus macaque model of Asian-lineage Zika virus infection. Nat. Commun. 7, 12204 (2016).

  70. 70.

    Osuna, C. E. et al. Zika viral dynamics and shedding in rhesus and cynomolgus macaques. Nat. Med. 22, 1448–1455 (2016).

  71. 71.

    Aliota, M. T. et al. Heterologous protection against Asian Zika virus challenge in rhesus macaques. PLoS Negl. Trop. Dis. 10, e0005168 (2016).

  72. 72.

    Koide, F. et al. Development of a Zika virus infection model in cynomolgus macaques. Front. Microbiol. 7, 2028 (2016).

  73. 73.

    Chiu, C. Y. et al. Experimental Zika virus inoculation in a new world monkey model reproduces key features of the human infection. Sci. Rep. 7, 17126 (2017).

  74. 74.

    Li, X. F. et al. Characterization of a 2016 clinical isolate of Zika virus in non-human primates. EBioMedicine 12, 170–177 (2016).

  75. 75.

    McCracken, M. K. et al. Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques. PLoS Pathog. 13, e1006487 (2017).

  76. 76.

    George, J. et al. Prior exposure to Zika virus significantly enhances peak dengue-2 viremia in rhesus macaques. Sci. Rep. 7, 10498 (2017).

  77. 77.

    Driggers, R. W. et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N. Engl. J. Med. 374, 2142–2151 (2016).

  78. 78.

    Adams Waldorf, K. M. et al. Fetal brain lesions after subcutaneous inoculation of Zika virus in a pregnant nonhuman primate. Nat. Med. 22, 1256–1259 (2016).

  79. 79.

    Nguyen, S. M. et al. Highly efficient maternal–fetal Zika virus transmission in pregnant rhesus macaques. PLoS Pathog. 13, e1006378 (2017).

  80. 80.

    Martinot, A. J. et al. Fetal neuropathology in Zika virus-infected pregnant female rhesus monkeys. Cell 173, 1111–1122 (2018).

  81. 81.

    Dudley, D. M. et al. Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates. Nat. Med. (2018).

  82. 82.

    Morrison, T. E. & Diamond, M. S. Animal models of Zika virus infection, pathogenesis, and immunity. J. Virol. 91, e00009-17 (2017).

  83. 83.

    Abbink, P. et al. Therapeutic and protective efficacy of a dengue antibody against Zika infection in rhesus monkeys. Nat. Med. 24, 721–723 (2018).

  84. 84.

    Mavigner, M. et al. Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques. Sci. Transl. Med. 10, eaao6975 (2018).

  85. 85.

    Rossi, S. L. et al. Characterization of a novel murine model to study Zika virus. Am. J. Trop. Med. Hyg. 94, 1362–1369 (2016).

  86. 86.

    Tripathi, S. et al. A novel Zika virus mouse model reveals strain specific differences in virus pathogenesis and host inflammatory immune responses. PLoS Pathog. 13, e1006258 (2017).

  87. 87.

    Savidis, G. et al. The IFITMs inhibit Zika virus replication. Cell Rep. 15, 2323–2330 (2016).

  88. 88.

    Monel, B. et al. Zika virus induces massive cytoplasmic vacuolization and paraptosis-like death in infected cells. EMBO J. 36, 1653–1668 (2017).

  89. 89.

    Van der Hoek, K. H. et al. Viperin is an important host restriction factor in control of Zika virus infection. Sci. Rep. 7, 4475 (2017).

  90. 90.

    Bowen, J. R. et al. Zika virus antagonizes type I interferon responses during infection of human dendritic cells. PLoS Pathog. 13, e1006164 (2017).

  91. 91.

    Sun, X. et al. Transcriptional changes during naturally acquired Zika virus infection render dendritic cells highly conducive to viral replication. Cell Rep. 21, 3471–3482 (2017).

  92. 92.

    Grant, A. et al. Zika virus targets human STAT2 to inhibit type I interferon signaling. Cell Host Microbe 19, 882–890 (2016). A study that explains in part how ZIKV evades the interferon response in humans but not mice.

  93. 93.

    Kumar, A. et al. Zika virus inhibits type-I interferon production and downstream signaling. EMBO Rep. 17, 1766–1775 (2016).

  94. 94.

    Ding, Q. et al. Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease. Proc. Natl Acad. Sci. USA 115, E6310–E6318 (2018).

  95. 95.

    Xia, H. et al. An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. Nat. Commun. 9, 414 (2018).

  96. 96.

    Donald, C. L. et al. Full genome sequence and sfRNA Interferon antagonist activity of Zika virus from Recife, Brazil. PLoS Negl. Trop. Dis. 10, e0005048 (2016).

  97. 97.

    Zhu, Z. et al. Zika virus has oncolytic activity against glioblastoma stem cells. J. Exp. Med. 214, 2843–2857 (2017).

  98. 98.

    Khan, S. et al. Dampened antiviral immunity to intravaginal exposure to RNA viral pathogens allows enhanced viral replication. J. Exp. Med. 213, 2913–2929 (2016).

  99. 99.

    Rogers, T. F. et al. Zika virus activates de novo and cross-reactive memory B cell responses in dengue-experienced donors. Sci. Immunol. 2, eaan6809 (2017).

  100. 100.

    Ricciardi, M. J. et al. Ontogeny of the B- and T-cell response in a primary Zika virus infection of a dengue-naïve individual during the 2016 outbreak in Miami, FL. PLoS Negl. Trop. Dis. 11, e0006000 (2017).

  101. 101.

    Dowd, K. A. et al. Broadly neutralizing activity of Zika virus–immune sera identifies a single viral serotype. Cell Rep. 16, 1485–1491 (2016).

  102. 102.

    Priyamvada, L., Suthar, M. S., Ahmed, R. & Wrammert, J. Humoral immune responses against Zika virus infection and the importance of preexisting flavivirus immunity. J. Infect. Dis. 216, S906–S911 (2017).

  103. 103.

    Stettler, K. et al. Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection. Science 353, 823–826 (2016).

  104. 104.

    Sapparapu, G. et al. Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice. Nature 540, 443–447 (2016). First two papers 103 , 104 describing neutralizing human monoclonal antibodies against ZIKV.

  105. 105.

    Lai, L. et al. Innate, T-, and B-cell responses in acute human Zika patients. Clin. Infect. Dis. 66, 1–10 (2018).

  106. 106.

    Priyamvada, L. et al. Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus. Proc. Natl Acad. Sci. USA 113, 7852–7857 (2016).

  107. 107.

    Zhao, H. et al. Structural basis of Zika virus-specific antibody protection. Cell 166, 1016–1027 (2016).

  108. 108.

    Swanstrom, J. A. et al. Dengue Virus envelope dimer epitope monoclonal antibodies isolated from dengue patients are protective against Zika virus. MBio 7, e01123-16 (2016).

  109. 109.

    Collins, M. H. et al. Lack of durable cross-neutralizing antibodies against Zika virus from dengue virus infection. Emerg. Infect. Dis. 23, 773–781 (2017).

  110. 110.

    Rouvinski, A. et al. Recognition determinants of broadly neutralizing human antibodies against dengue viruses. Nature 520, 109–113 (2015).

  111. 111.

    Wang, J. et al. A Human bi-specific antibody against Zika virus with high therapeutic potential. Cell 171, 229–241 (2017).

  112. 112.

    Yu, L. et al. Delineating antibody recognition against Zika virus during natural infection. JCI Insight 2, 93042 (2017).

  113. 113.

    Wang, Q. et al. Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus. Sci. Transl. Med. 8, 369ra179 (2016).

  114. 114.

    Pardy, R. D. et al. Analysis of the T cell response to Zika virus and identification of a novel CD8+ T cell epitope in immunocompetent mice. PLoS Pathog. 13, e1006184 (2017).

  115. 115.

    Elong Ngono, A. et al. Mapping and role of the CD8+ T cell response during primary Zika virus infection in mice. Cell Host Microbe 21, 35–46 (2017).

  116. 116.

    Huang, H. et al. CD8+ T cell immune response in immunocompetent mice during Zika virus infection. J. Virol. 91, e00900-17 (2017).

  117. 117.

    Wen, J. et al. Identification of Zika virus epitopes reveals immunodominant and protective roles for dengue virus cross-reactive CD8+ T cells. Nat. Microbiol. 2, 17036 (2017).

  118. 118.

    Manangeeswaran, M., Ireland, D. D. & Verthelyi, D. Zika (PRVABC59) infection is associated with T cell infiltration and neurodegeneration in CNS of immunocompetent neonatal C57BL/6 mice. PLoS Pathog. 12, e1006004 (2016).

  119. 119.

    Jurado, K. A. et al. Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice. Nat. Microbiol. 3, 141–147 (2018).

  120. 120.

    Cimini, E. et al. Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells. Sci. Rep. 7, 6313 (2017).

  121. 121.

    Grifoni, A. et al. Prior Dengue virus exposure shapes T cell immunity to Zika virus in humans. J. Virol. e01469-17 (2017).

  122. 122.

    Weiskopf, D. et al. Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells. Proc. Natl Acad. Sci. USA 110, E2046–E2053 (2013). (2013).

  123. 123.

    Liu, Y. et al. Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature 545, 482–486 (2017).

  124. 124.

    Yuan, L. et al. A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science 358, 933–936 (2017). Two papers 123 , 124 describe the genetic changes in epidemic ZIKV strains that may explain altered epidemiology and pathogenicity.

  125. 125.

    Klase, Z. A. et al. Zika fetal neuropathogenesis: etiology of a viral syndrome. PLoS Negl. Trop. Dis. 10, e0004877 (2016).

  126. 126.

    Chavali, P. L. et al. Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication. Science 357, 83–88 (2017).

  127. 127.

    Dejnirattisai, W. et al. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with Zika virus. Nat. Immunol. 17, 1102–1108 (2016).

  128. 128.

    Bardina, S. V. et al. Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity. Science 356, 175–180 (2017).

  129. 129.

    Terzian, A. C. B. et al. Viral load and cytokine response profile does not support antibody-dependent enhancement in dengue-primed Zika virus-infected patients. Clin. Infect. Dis. 65, 1260–1265 (2017).

  130. 130.

    Halai, U. A. et al. Maternal Zika virus disease severity, virus load, prior dengue antibodies, and their relationship to birth outcomes. Clin. Infect. Dis. 65, 877–883 (2017).

  131. 131.

    Dowd, K. A. et al. Rapid development of a DNA vaccine for Zika virus. Science 354, 237–240 (2016).

  132. 132.

    Tebas, P. et al. Safety and immunogenicity of an anti-Zika virus DNA vaccine — preliminary report. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1708120 (2017).

  133. 133.

    Abbink, P. et al. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science 353, 1129–1132 (2016).

  134. 134.

    Larocca, R. A. et al. Vaccine protection against Zika virus from Brazil. Nature 536, 474–478 (2016).

  135. 135.

    Gaudinski, M. R. et al. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials. Lancet 391, 552–562 (2018). Five papers 131,132,133,134, 135 describe the DNA and inactivated vaccine platforms under development against ZIKV.

  136. 136.

    Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543, 248–251 (2017).

  137. 137.

    Richner, J. M. et al. Modified mRNA vaccines protect against Zika virus infection. Cell 168, 1114–1125 (2017).

  138. 138.

    Richner, J. M. et al. Vaccine mediated protection against Zika virus-induced congenital disease. Cell 170, 273–283 (2017). Three papers 136,137, 138 describe the use of mRNA-based vaccines against ZIKV.

  139. 139.

    Abbink, P. et al. Durability and correlates of vaccine protection against Zika virus in rhesus monkeys. Sci. Transl. Med. 9, eaao4163 (2017).

  140. 140.

    Xie, X. et al. Understanding Zika virus stability and developing a chimeric vaccine through functional analysis. MBio 8, e02134-16 (2017).

  141. 141.

    Shan, C. et al. A live-attenuated Zika virus vaccine candidate induces sterilizing immunity in mouse models. Nat. Med. 23, 763–767 (2017).

  142. 142.

    Shan, C. et al. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage. Nat. Commun. 8, 676 (2017).

  143. 143.

    Betancourt, D., de Queiroz, N. M., Xia, T., Ahn, J. & Barber, G. N. Cutting edge: innate immune augmenting vesicular stomatitis virus expressing Zika virus proteins confers protective immunity. J. Immunol. 198, 3023–3028 (2017).

  144. 144.

    Prow, N. A. et al. A vaccinia-based single vector construct multi-pathogen vaccine protects against both Zika and chikungunya viruses. Nat. Commun. 9, 1230 (2018).

  145. 145.

    Brault, A. C. et al. A Zika vaccine targeting NS1 protein protects immunocompetent adult mice in a lethal challenge model. Sci. Rep. 7, 14769 (2017).

  146. 146.

    Salvo, M. A., Kingstad-Bakke, B., Salas-Quinchucua, C., Camacho, E. & Osorio, J. E. Zika virus like particles elicit protective antibodies in mice. PLoS Negl. Trop. Dis. 12, e0006210 (2018).

  147. 147.

    Bayer, A. et al. Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling. Placenta 61, 33–38 (2018).

Download references

Acknowledgements

This work was supported by NIH grants (R01 AI073755, R01 AI104972, U19 AI083019 and R01 HD091218) and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. We thank E. Tyler (NIH) for assistance with figure preparation of virion models. This publication is the responsibility of the authors and does not necessarily represent the official view of the NIH.

Reviewer information

Nature thanks J. Jung and H. Tang for their contribution to the peer review of this work.

Author information

Affiliations

  1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    • Theodore C. Pierson
  2. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    • Michael S. Diamond
  3. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA

    • Michael S. Diamond
  4. Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA

    • Michael S. Diamond
  5. Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA

    • Michael S. Diamond

Authors

  1. Search for Theodore C. Pierson in:

  2. Search for Michael S. Diamond in:

Contributions

T.C.P. and M.S.D. conceived and wrote the review.

Competing interests

M.S.D. is a consultant for Inbios and on the Scientific Advisory Board of Moderna. T.C.P. is a co-inventor of NIAID ZIKV vaccine candidates.

Corresponding authors

Correspondence to Theodore C. Pierson or Michael S. Diamond.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/s41586-018-0446-y

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.