Journal of Microbiology

, Volume 55, Issue 3, pp 204–219 | Cite as

Zika virus: An emerging flavivirus

  • Sang-Im Yun
  • Young-Min LeeEmail author
Review Emerging and Re-emerging Viral Disease and Vaccines


Zika virus (ZIKV) is a previously little-known flavivirus closely related to Japanese encephalitis, West Nile, dengue, and yellow fever viruses, all of which are primarily transmitted by blood-sucking mosquitoes. Since its discovery in Uganda in 1947, ZIKV has continued to expand its geographic range, from equatorial Africa and Asia to the Pacific Islands, then further afield to South and Central America and the Caribbean. Currently, ZIKV is actively circulating not only in much of Latin America and its neighbors but also in parts of the Pacific Islands and Southeast Asia. Although ZIKV infection generally causes only mild symptoms in some infected individuals, it is associated with a range of neuroimmunological disorders, including Guillain-Barré syndrome, meningoencephalitis, and myelitis. Recently, maternal ZIKV infection during pregnancy has been linked to neonatal malformations, resulting in various degrees of congenital abnormalities, microcephaly, and even abortion. Despite its emergence as an important public health problem, however, little is known about ZIKV biology, and neither vaccine nor drug is available to control ZIKV infection. This article provides a brief introduction to ZIKV with a major emphasis on its molecular virology, in order to help facilitate the development of diagnostics, therapeutics, and vaccines.


Zika virus flavivirus mosquito-borne virus arbovirus microcephaly Guillain-Barré syndrome replication pathogenesis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acosta, E.G., Castilla, V., and Damonte, E.B. 2008. Functional entry of dengue virus into Aedes albopictus mosquito cells is dependent on clathrin-mediated endocytosis. J. Gen. Virol. 89, 474–484.PubMedCrossRefGoogle Scholar
  2. Adekolu-John, E.O. and Fagbami, A.H. 1983. Arthropod-borne virus antibodies in sera of residents of Kainji Lake Basin, Nigeria 1980. Trans. R. Soc. Trop. Med. Hyg. 77, 149–151.PubMedCrossRefGoogle Scholar
  3. Adiga, R. 2016. Phylogenetic analysis of the NS5 gene of Zika virus. J. Med. Virol. 88, 1821–1826.PubMedCrossRefGoogle Scholar
  4. Akiyama, B.M., Laurence, H.M., Massey, A.R., Costantino, D.A., Xie, X., Yang, Y., Shi, P.Y., Nix, J.C., Beckham, J.D., and Kieft, J.S. 2016. Zika virus produces noncoding RNAs using a multiseudoknot structure that confounds a cellular exonuclease. Science 354, 1148–1152.PubMedCrossRefGoogle Scholar
  5. Alera, M.T., Hermann, L., Tac-An, I.A., Klungthong, C., Rutvisuttinunt, W., Manasatienkij, W., Villa, D., Thaisomboonsuk, B., Velasco, J.M., Chinnawirotpisan, P., et al. 2015. Zika virus infection, Philippines, 2012. Emerg. Infect. Dis. 21, 722–724.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Allison, S.L., Schalich, J., Stiasny, K., Mandl, C.W., and Heinz, F.X. 2001. Mutational evidence for an internal fusion peptide in flavivirus envelope protein E. J. Virol. 75, 4268–4275.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Allison, S.L., Schalich, J., Stiasny, K., Mandl, C.W., Kunz, C., and Heinz, F.X. 1995. Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J. Virol. 69, 695–700.PubMedPubMedCentralGoogle Scholar
  8. Allison, S.L., Stiasny, K., Stadler, K., Mandl, C.W., and Heinz, F.X. 1999. Mapping of functional elements in the stem-anchor region of tick-borne encephalitis virus envelope protein E. J. Virol. 73, 5605–5612.PubMedPubMedCentralGoogle Scholar
  9. Alvarez, D.E., Lodeiro, M.F., Luduena, S.J., Pietrasanta, L.I., and Gamarnik, A.V. 2005. Long-range RNA-RNA interactions circularize the dengue virus genome. J. Virol. 79, 6631–6643.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Amberg, S.M., Nestorowicz, A., McCourt, D.W., and Rice, C.M. 1994. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J. Virol. 68, 3794–3802.PubMedPubMedCentralGoogle Scholar
  11. Apte-Sengupta, S., Sirohi, D., and Kuhn, R.J. 2014. Coupling of replication and assembly in flaviviruses. Curr. Opin. Virol. 9, 134–142.PubMedCrossRefGoogle Scholar
  12. Assenberg, R., Mastrangelo, E., Walter, T.S., Verma, A., Milani, M., Owens, R.J., Stuart, D.I., Grimes, J.M., and Mancini, E.J. 2009. Crystal structure of a novel conformational state of the flavivirus NS3 protein: implications for polyprotein processing and viral replication. J. Virol. 83, 12895–12906.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Barba-Spaeth, G., Dejnirattisai, W., Rouvinski, A., Vaney, M.C., Medits, I., Sharma, A., Simon-Loriere, E., Sakuntabhai, A., Cao-Lormeau, V.M., Haouz, A., et al. 2016. Structural basis of potent Zika-dengue virus antibody cross-neutralization. Nature 536, 48–53.PubMedCrossRefGoogle Scholar
  14. Baronti, C., Piorkowski, G., Charrel, R.N., Boubis, L., Leparc- Goffart, I., and de Lamballerie, X. 2014. Complete coding sequence of Zika virus from a French Polynesia outbreak in 2013. Genome Announc. 2, e00500–14.CrossRefGoogle Scholar
  15. Barreto-Vieira, D.F., Barth, O.M., Silva, M.A., Santos, C.C., Santos Ada, S., Filho, F.J., and Filippis, A.M. 2016. Ultrastructure of Zika virus particles in cell cultures. Mem. Inst. Oswaldo Cruz 111, 532–534.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Barzon, L., Pacenti, M., Berto, A., Sinigaglia, A., Franchin, E., Lavezzo, E., Brugnaro, P., and Palu, G. 2016. Isolation of infectious Zika virus from saliva and prolonged viral RNA shedding in a traveller returning from the Dominican Republic to Italy, January 2016. Euro Surveill. 21, 30159.CrossRefPubMedGoogle Scholar
  17. Beasley, D.W. and Barrett, A.D. 2002. Identification of neutralizing epitopes within structural domain III of the West Nile virus envelope protein. J. Virol. 76, 13097–13100.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Beasley, D.W., Whiteman, M.C., Zhang, S., Huang, C.Y., Schneider, B.S., Smith, D.R., Gromowski, G.D., Higgs, S., Kinney, R.M., and Barrett, A.D. 2005. Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains. J. Virol. 79, 8339–8347.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Berthet, N., Nakoune, E., Kamgang, B., Selekon, B., Descorps-Declere, S., Gessain, A., Manuguerra, J.C., and Kazanji, M. 2014. Molecular characterization of three Zika flaviviruses obtained from sylvatic mosquitoes in the Central African Republic. Vector Borne Zoonotic Dis. 14, 862–865.PubMedCrossRefGoogle Scholar
  20. Besnard, M., Lastere, S., Teissier, A., Cao-Lormeau, V., and Musso, D. 2014. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill. 19, 20751.PubMedCrossRefGoogle Scholar
  21. Bidet, K., Dadlani, D., and Garcia-Blanco, M.A. 2014. G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA. PLoS Pathog. 10, e1004242.CrossRefGoogle Scholar
  22. Bidet, K. and Garcia-Blanco, M.A. 2014. Flaviviral RNAs: weapons and targets in the war between virus and host. Biochem. J. 462, 215–230.PubMedCrossRefGoogle Scholar
  23. Bogoch, I.I., Brady, O.J., Kraemer, M.U., German, M., Creatore, M.I., Kulkarni, M.A., Brownstein, J.S., Mekaru, S.R., Hay, S.I., Groot, E., et al. 2016. Anticipating the international spread of Zika virus from Brazil. Lancet 387, 335–336.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Bollati, M., Alvarez, K., Assenberg, R., Baronti, C., Canard, B., Cook, S., Coutard, B., Decroly, E., de Lamballerie, X., Gould, E.A., et al. 2010. Structure and functionality in flavivirus NS-proteins: perspectives for drug design. Antiviral Res. 87, 125–148.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Bressanelli, S., Stiasny, K., Allison, S.L., Stura, E.A., Duquerroy, S., Lescar, J., Heinz, F.X., and Rey, F.A. 2004. Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation. EMBO J. 23, 728–738.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Brinton, M.A. 2013. Replication cycle and molecular biology of the West Nile virus. Viruses 6, 13–53.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Brinton, M.A. and Basu, M. 2015. Functions of the 3’ and 5’ genome RNA regions of members of the genus Flavivirus. Virus Res. 206, 108–119.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Buathong, R., Hermann, L., Thaisomboonsuk, B., Rutvisuttinunt, W., Klungthong, C., Chinnawirotpisan, P., Manasatienkij, W., Nisalak, A., Fernandez, S., Yoon, I.K., et al. 2015. Detection of Zika virus infection in Thailand, 2012-2014. Am. J. Trop. Med. Hyg. 93, 380–383.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Campos, G.S., Bandeira, A.C., and Sardi, S.I. 2015. Zika virus outbreak, Bahia, Brazil. Emerg. Infect. Dis. 21, 1885–1886.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Cao-Lormeau, V.M., Blake, A., Mons, S., Lastere, S., Roche, C., Vanhomwegen, J., Dub, T., Baudouin, L., Teissier, A., Larre, P., et al. 2016. Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 387, 1531–1539.PubMedCrossRefGoogle Scholar
  31. Cao-Lormeau, V.M. and Musso, D. 2014. Emerging arboviruses in the Pacific. Lancet 384, 1571–1572.PubMedCrossRefGoogle Scholar
  32. Cao-Lormeau, V.M., Roche, C., Teissier, A., Robin, E., Berry, A.L., Mallet, H.P., Sall, A.A., and Musso, D. 2014. Zika virus, French Polynesia, South Pacific, 2013. Emerg. Infect. Dis. 20, 1085–1086.PubMedPubMedCentralGoogle Scholar
  33. Cardoso, C.W., Paploski, I.A., Kikuti, M., Rodrigues, M.S., Silva, M.M., Campos, G.S., Sardi, S.I., Kitron, U., Reis, M.G., and Ribeiro, G.S. 2015. Outbreak of exanthematous illness associated with Zika, chikungunya, and dengue viruses, Salvador, Brazil. Emerg. Infect. Dis. 21, 2274–2276.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Castle, E., Leidner, U., Nowak, T., Wengler, G., and Wengler, G. 1986. Primary structure of the West Nile flavivirus genome region coding for all nonstructural proteins. Virology 149, 10–26.PubMedCrossRefGoogle Scholar
  35. Castle, E., Nowak, T., Leidner, U., Wengler, G., and Wengler, G. 1985. Sequence analysis of the viral core protein and the membrane-associated proteins V1 and NV2 of the flavivirus West Nile virus and of the genome sequence for these proteins. Virology 145, 227–236.PubMedCrossRefGoogle Scholar
  36. Cauchemez, S., Besnard, M., Bompard, P., Dub, T., Guillemette-Artur, P., Eyrolle-Guignot, D., Salje, H., van Kerkhove, M.D., Abadie, V., Garel, C., et al. 2016. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet 387, 2125–2132.PubMedPubMedCentralCrossRefGoogle Scholar
  37. CDC. 2016. All countries and territories with active Zika virus transmission. Centers for Disease Control and Prevention, Atlanta, Georgia. December 16, 2016. html.Google Scholar
  38. CDC. 2017a. Case counts in the US. Centers for Disease Control and Prevention, Atlanta, Georgia. January 19, 2017. https://www. Scholar
  39. CDC. 2017b. Outcomes of pregnancies with laboratory evidence of possible Zika virus infection in the United States. Centers for Disease Control and Prevention, Atlanta, Georgia. January 19, 2017. Scholar
  40. CDC. 2017c. Zika cases reported in the United States. Centers for Disease Control and Prevention, Atlanta, Georgia. January 19, 2017. Scholar
  41. Chambers, T.J., Hahn, C.S., Galler, R., and Rice, C.M. 1990a. Flavivirus genome organization, expression, and replication. Annu. Rev. Microbiol. 44, 649–688.PubMedCrossRefGoogle Scholar
  42. Chambers, T.J., McCourt, D.W., and Rice, C.M. 1990b. Production of yellow fever virus proteins in infected cells: identification of discrete polyprotein species and analysis of cleavage kinetics using region-specific polyclonal antisera. Virology 177, 159–174.PubMedCrossRefGoogle Scholar
  43. Chang, R.Y., Hsu, T.W., Chen, Y.L., Liu, S.F., Tsai, Y.J., Lin, Y.T., Chen, Y.S., and Fan, Y.H. 2013. Japanese encephalitis virus noncoding RNA inhibits activation of interferon by blocking nuclear translocation of interferon regulatory factor 3. Vet. Microbiol. 166, 11–21.PubMedCrossRefGoogle Scholar
  44. Chapman, E.G., Moon, S.L., Wilusz, J., and Kieft, J.S. 2014. RNA structures that resist degradation by Xrn1 produce a pathogenic dengue virus RNA. Elife 3, e01892.CrossRefGoogle Scholar
  45. Charley, P.A. and Wilusz, J. 2016. Standing your ground to exoribonucleases: function of Flavivirus long non-coding RNAs. Virus Res. 212, 70–77.PubMedCrossRefGoogle Scholar
  46. Chatel-Chaix, L. and Bartenschlager, R. 2014. Dengue virus-and hepatitis C virus-induced replication and assembly compartments: the enemy inside–caught in the web. J. Virol. 88, 5907–5911.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Chen, Y., Maguire, T., Hileman, R.E., Fromm, J.R., Esko, J.D., Linhardt, R.J., and Marks, R.M. 1997. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat. Med. 3, 866–871.PubMedCrossRefGoogle Scholar
  48. Chu, J.J., Leong, P.W., and Ng, M.L. 2006. Analysis of the endocytic pathway mediating the infectious entry of mosquito-borne flavivirus West Nile into Aedes albopictus mosquito (C6/36) cells. Virology 349, 463–475.PubMedCrossRefGoogle Scholar
  49. Chu, J.J. and Ng, M.L. 2004. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J. Virol. 78, 10543–10555.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Clarke, B.D., Roby, J.A., Slonchak, A., and Khromykh, A.A. 2015. Functional non-coding RNAs derived from the flavivirus 3’ untranslated region. Virus Res. 206, 53–61.PubMedCrossRefGoogle Scholar
  51. Clyde, K., Barrera, J., and Harris, E. 2008. The capsid-coding region hairpin element (cHP) is a critical determinant of dengue virus and West Nile virus RNA synthesis. Virology 379, 314–323.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Clyde, K. and Harris, E. 2006. RNA secondary structure in the coding region of dengue virus type 2 directs translation start codon selection and is required for viral replication. J. Virol. 80, 2170–2182.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Coloma, J., Jain, R., Rajashankar, K.R., Garcia-Sastre, A., and Aggarwal, A.K. 2016. Structures of NS5 methyltransferase from Zika virus. Cell Rep. 16, 3097–3102.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Corver, J., Ortiz, A., Allison, S.L., Schalich, J., Heinz, F.X., and Wilschut, J. 2000. Membrane fusion activity of tick-borne encephalitis virus and recombinant subviral particles in a liposomal model system. Virology 269, 37–46.PubMedCrossRefGoogle Scholar
  55. Coutard, B., Barral, K., Lichiere, J., Selisko, B., Martin, B., Aouadi, W., Ortiz Lombardia, M., Debart, F., Vasseur, J.J., Guillemot, J.C., et al. 2016. The Zika virus methyltransferase: structure and functions for drug design perspectives. J. Virol. pii: JVI.02202–16. doi: 10.1128/JVI.02202-16.Google Scholar
  56. Cox, B.D., Stanton, R.A., and Schinazi, R.F. 2015. Predicting Zika virus structural biology: challenges and opportunities for intervention. Antivir. Chem. Chemother. 24, 118–126.PubMedCrossRefGoogle Scholar
  57. Crill, W.D. and Roehrig, J.T. 2001. Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. J. Virol. 75, 7769–7773.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Cunha, M.S., Esposito, D.L., Rocco, I.M., Maeda, A.Y., Vasami, F.G., Nogueira, J.S., de Souza, R.P., Suzuki, A., Addas-Carvalho, M., Barjas-Castro Mde, L., et al. 2016. First complete genome sequence of Zika virus (Flaviviridae, Flavivirus) from an autochthonous transmission in Brazil. Genome Announc. 4, e00032-16.CrossRefGoogle Scholar
  59. Daffis, S., Szretter, K.J., Schriewer, J., Li, J., Youn, S., Errett, J., Lin, T.Y., Schneller, S., Zust, R., Dong, H., et al. 2010. 2’-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 468, 452–456.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Dai, L., Song, J., Lu, X., Deng, Y.Q., Musyoki, A.M., Cheng, H., Zhang, Y., Yuan, Y., Song, H., Haywood, J., et al. 2016. Structures of the Zika virus envelope protein and its complex with a flavivirus broadly protective antibody. Cell Host Microbe 19, 696–704.PubMedCrossRefGoogle Scholar
  61. Dalrymple, N.A., Cimica, V., and Mackow, E.R. 2015. Dengue virus NS proteins inhibit RIG-I/MAVS signaling by blocking TBK1/IRF3 phosphorylation: dengue virus serotype 1 NS4A is a unique interferon-regulating virulence determinant. MBio 6, e00553–15.CrossRefGoogle Scholar
  62. Darwish, M.A., Hoogstraal, H., Roberts, T.J., Ahmed, I.P., and Omar, F. 1983. A sero-epidemiological survey for certain arboviruses (Togaviridae) in Pakistan. Trans. R. Soc. Trop. Med. Hyg. 77, 442–445.PubMedCrossRefGoogle Scholar
  63. Davis, W.G., Basu, M., Elrod, E.J., Germann, M.W., and Brinton, M.A. 2013. Identification of cis-acting nucleotides and a structural feature in West Nile virus 3’-terminus RNA that facilitate viral minus strand RNA synthesis. J. Virol. 87, 7622–7636.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Davis, W.G., Blackwell, J.L., Shi, P.Y., and Brinton, M.A. 2007. Interaction between the cellular protein eEF1A and the 3’-terminal stem-loop of West Nile virus genomic RNA facilitates viral minus-strand RNA synthesis. J. Virol. 81, 10172–10187.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Davis, C.W., Nguyen, H.Y., Hanna, S.L., Sanchez, M.D., Doms, R.W., and Pierson, T.C. 2006. West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection. J. Virol. 80, 1290–1301.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Dick, G.W. 1953. Epidemiological notes on some viruses isolated in Uganda; yellow fever, Rift Valley fever, Bwamba fever, West Nile, Mengo, Semliki forest, Bunyamwera, Ntaya, Uganda S and Zika viruses. Trans. R. Soc. Trop. Med. Hyg. 47, 13–48.PubMedCrossRefGoogle Scholar
  67. Dick, G.W., Kitchen, S.F., and Haddow, A.J. 1952. Zika virus. I. Isolations and serological specificity. Trans. R. Soc. Trop. Med. Hyg. 46, 509–520.PubMedCrossRefGoogle Scholar
  68. Dokland, T., Walsh, M., Mackenzie, J.M., Khromykh, A.A., Ee, K.H., and Wang, S. 2004. West Nile virus core protein; tetramer structure and ribbon formation. Structure 12, 1157–1163.PubMedCrossRefGoogle Scholar
  69. Dong, H., Fink, K., Zust, R., Lim, S.P., Qin, C.F., and Shi, P.Y. 2014. Flavivirus RNA methylation. J. Gen. Virol. 95, 763–778.PubMedCrossRefGoogle Scholar
  70. Dong, H., Zhang, B., and Shi, P.Y. 2008a. Flavivirus methyltransferase: a novel antiviral target. Antiviral Res. 80, 1–10.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Dong, H., Zhang, B., and Shi, P.Y. 2008b. Terminal structures of West Nile virus genomic RNA and their interactions with viral NS5 protein. Virology 381, 123–135.PubMedCrossRefGoogle Scholar
  72. Duffy, M.R., Chen, T.H., Hancock, W.T., Powers, A.M., Kool, J.L., Lanciotti, R.S., Pretrick, M., Marfel, M., Holzbauer, S., Dubray, C., et al. 2009. Zika virus outbreak on Yap Island, Federated States of Micronesia. N. Engl. J. Med. 360, 2536–2543.PubMedCrossRefGoogle Scholar
  73. Dupont-Rouzeyrol, M., O’Connor, O., Calvez, E., Daures, M., John, M., Grangeon, J.P., and Gourinat, A.C. 2015. Co-infection with Zika and dengue viruses in 2 patients, New Caledonia, 2014. Emerg. Infect. Dis. 21, 381–382.PubMedPubMedCentralCrossRefGoogle Scholar
  74. ECDC. 2014. Rapid risk assessment: Zika virus infection outbreak, French Polynesia. European Centre for Disease Prevention and Control, Stockholm, Sweden. February 14, 2014. http://ecdc.uropa. eu/en/publications/Publications/Zika-virus-French-Polynesiarapid-risk-assessment.pdf.Google Scholar
  75. ECDC. 2017. Current Zika transmission. European Centre for Disease Prevention and Control, Stockholm, Sweden. January 20, 2017. pages/zika-countries-with-transmission.aspx.Google Scholar
  76. Elghonemy, S., Davis, W.G., and Brinton, M.A. 2005. The majority of the nucleotides in the top loop of the genomic 3’ terminal stem loop structure are cis-acting in a West Nile virus infectious clone. Virology 331, 238–246.PubMedCrossRefGoogle Scholar
  77. Ellison, D.W., Ladner, J.T., Buathong, R., Alera, M.T., Wiley, M.R., Hermann, L., Rutvisuttinunt, W., Klungthong, C., Chinnawirotpisan, P., Manasatienkij, W., et al. 2016. Complete genome sequences of Zika virus strains isolated from the blood of patients in Thailand in 2014 and the Philippines in 2012. Genome Announc. 4, e00359-16.CrossRefGoogle Scholar
  78. Elshuber, S., Allison, S.L., Heinz, F.X., and Mandl, C.W. 2003. Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus. J. Gen. Virol. 84, 183–191.PubMedCrossRefGoogle Scholar
  79. Fagbami, A. 1977. Epidemiological investigations on arbovirus infections at Igbo-Ora, Nigeria. Trop. Geogr. Med. 29, 187–191.PubMedGoogle Scholar
  80. Fagbami, A.H. 1979. Zika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo State. J. Hyg. 83, 213–219.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Falgout, B., Chanock, R., and Lai, C.J. 1989. Proper processing of dengue virus nonstructural glycoprotein NS1 requires the N-terminal hydrophobic signal sequence and the downstream nonstructural protein NS2A. J. Virol. 63, 1852–1860.PubMedPubMedCentralGoogle Scholar
  82. Falgout, B. and Markoff, L. 1995. Evidence that flavivirus NS1-NS2A cleavage is mediated by a membrane-bound host protease in the endoplasmic reticulum. J. Virol. 69, 7232–7243.PubMedPubMedCentralGoogle Scholar
  83. Fan, Y.H., Nadar, M., Chen, C.C., Weng, C.C., Lin, Y.T., and Chang, R.Y. 2011. Small noncoding RNA modulates Japanese encephalitis virus replication and translation in trans. Virol. J. 8, 492.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Faria, N.R., Azevedo Rdo, S., Kraemer, M.U., Souza, R., Cunha, M.S., Hill, S.C., Theze, J., Bonsall, M.B., Bowden, T.A., Rissanen, I., et al. 2016. Zika virus in the Americas: early epidemiological and genetic findings. Science 352, 345–349.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Fauci, A.S. and Morens, D.M. 2016. Zika virus in the Americas–yet another arbovirus threat. N. Engl. J. Med. 374, 601–604.PubMedCrossRefGoogle Scholar
  86. Filomatori, C.V., Lodeiro, M.F., Alvarez, D.E., Samsa, M.M., Pietrasanta, L., and Gamarnik, A.V. 2006. A 5’ RNA element promotes dengue virus RNA synthesis on a circular genome. Genes Dev. 20, 2238–2249.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Firth, A.E. and Atkins, J.F. 2009. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1’ may derive from ribosomal frameshifting. Virol. J. 6, 14.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Fonseca, K., Meatherall, B., Zarra, D., Drebot, M., MacDonald, J., Pabbaraju, K., Wong, S., Webster, P., Lindsay, R., and Tellier, R. 2014. First case of Zika virus infection in a returning Canadian traveler. Am. J. Trop. Med. Hyg. 91, 1035–1038.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Friebe, P. and Harris, E. 2010. Interplay of RNA elements in the dengue virus 5’ and 3’ ends required for viral RNA replication. J. Virol. 84, 6103–6118.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Friebe, P., Shi, P.Y., and Harris, E. 2011. The 5’ and 3’ downstream AUG region elements are required for mosquito-borne flavivirus RNA replication. J. Virol. 85, 1900–1905.PubMedCrossRefGoogle Scholar
  91. Funk, A., Truong, K., Nagasaki, T., Torres, S., Floden, N., Balmori Melian, E., Edmonds, J., Dong, H., Shi, P.Y., and Khromykh, A.A. 2010. RNA structures required for production of subgenomic flavivirus RNA. J. Virol. 84, 11407–11417.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Gebhard, L.G., Filomatori, C.V., and Gamarnik, A.V. 2011. Functional RNA elements in the dengue virus genome. Viruses 3, 1739–1756.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Geser, A., Henderson, B.E., and Christensen, S. 1970. A multipurpose serological survey in Kenya. 2. Results of arbovirus serological tests. Bull. World Health Organ. 43, 539–552.PubMedGoogle Scholar
  94. Gillespie, L.K., Hoenen, A., Morgan, G., and Mackenzie, J.M. 2010. The endoplasmic reticulum provides the membrane platform for biogenesis of the flavivirus replication complex. J. Virol. 84, 10438–10447.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Giovanetti, M., Faria, N.R., Nunes, M.R., de Vasconcelos, J.M., Lourenco, J., Rodrigues, S.G., Vianez, J.L.Jr., da Silva, S.P., Lemos, P.S., Tavares, F.N., et al. 2016. Zika virus complete genome from Salvador, Bahia, Brazil. Infect. Genet. Evol. 41, 142–145.PubMedCrossRefGoogle Scholar
  96. Goertz, G.P., Fros, J.J., Miesen, P., Vogels, C.B., van der Bent, M.L., Geertsema, C., Koenraadt, C.J., van Rij, R.P., van Oers, M.M., and Pijlman, G.P. 2016. Noncoding subgenomic flavivirus RNA is processed by the mosquito RNA interference machinery and determines West Nile virus transmission by Culex pipiens mosquitoes. J. Virol. 90, 10145–10159.PubMedCrossRefGoogle Scholar
  97. Gomila, R.C., Martin, G.W., and Gehrke, L. 2011. NF90 binds the dengue virus RNA 3’ terminus and is a positive regulator of dengue virus replication. PLoS One 6, e16687.CrossRefGoogle Scholar
  98. Gould, E.A. and Solomon, T. 2008. Pathogenic flaviviruses. Lancet 371, 500–509.PubMedCrossRefGoogle Scholar
  99. Gubler, D.J., Kuno, G., and Markoff, L. 2007. Flaviviruses, pp. 1153–1252. In Knipe, D.M., Howley, P.M., Griffin, D.E., Lamb, R.A., Martin, M.A., Roizman, B., and Straus, S.E. (eds.), Fields Virology. Lippincott Williams & Wilkins Publishers, Philadelphia, Pennsylvania, USA.Google Scholar
  100. Guirakhoo, F., Heinz, F.X., Mandl, C.W., Holzmann, H., and Kunz, C. 1991. Fusion activity of flaviviruses: comparison of mature and immature (prM-containing) tick-borne encephalitis virions. J. Gen. Virol. 72, 1323–1329.PubMedCrossRefGoogle Scholar
  101. Guo, J.T., Hayashi, J., and Seeger, C. 2005. West Nile virus inhibits the signal transduction pathway of alpha interferon. J. Virol. 79, 1343–1350.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Haddow, A.D., Schuh, A.J., Yasuda, C.Y., Kasper, M.R., Heang, V., Huy, R., Guzman, H., Tesh, R.B., and Weaver, S.C. 2012. Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage. PLoS Negl. Trop. Dis. 6, e1477.CrossRefGoogle Scholar
  103. Hamel, R., Dejarnac, O., Wichit, S., Ekchariyawat, P., Neyret, A., Luplertlop, N., Perera-Lecoin, M., Surasombatpattana, P., Talignani, L., Thomas, F., et al. 2015. Biology of Zika virus infection in human skin cells. J. Virol. 89, 8880–8896.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Hammon, W.M., Schrack, W.D.Jr., and Sather, G.E. 1958. Serological survey for a arthropod-borne virus infections in the Philippines. Am. J. Trop. Med. Hyg. 7, 323–328.PubMedGoogle Scholar
  105. Harrison, S.C. 2015. Viral membrane fusion. Virology 479-480, 498–507.Google Scholar
  106. Hayes, E.B. 2009. Zika virus outside Africa. Emerg. Infect. Dis. 15, 1347–1350.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Heang, V., Yasuda, C.Y., Sovann, L., Haddow, A.D., Travassos da Rosa, A.P., Tesh, R.B., and Kasper, M.R. 2012. Zika virus infection, Cambodia, 2010. Emerg. Infect. Dis. 18, 349–351.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Hennessey, M., Fischer, M., and Staples, J.E. 2016. Zika virus spreads to new areas–region of the Americas, May 2015-January 2016. MMWR Morb. Mortal. Wkly. Rep. 65, 55–58.PubMedCrossRefGoogle Scholar
  109. Hori, H. and Lai, C.J. 1990. Cleavage of dengue virus NS1-NS2A requires an octapeptide sequence at the C terminus of NS1. J. Virol. 64, 4573–4577.PubMedPubMedCentralGoogle Scholar
  110. Hsu, N.Y., Ilnytska, O., Belov, G., Santiana, M., Chen, Y.H., Takvorian, P.M., Pau, C., van der Schaar, H., Kaushik-Basu, N., Balla, T., et al. 2010. Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell 141, 799–811.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Iglesias, N.G. and Gamarnik, A.V. 2011. Dynamic RNA structures in the dengue virus genome. RNA Biol. 8, 249–257.PubMedCrossRefGoogle Scholar
  112. Jain, R., Coloma, J., Garcia-Sastre, A., and Aggarwal, A.K. 2016. Structure of the NS3 helicase from Zika virus. Nat. Struct. Mol. Biol. 23, 752–754.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Jan, C., Languillat, G., Renaudet, J., and Robin, Y. 1978. A serological survey of arboviruses in Gabon. Bull. Soc. Pathol. Exot. Filiales 71, 140–146.PubMedGoogle Scholar
  114. Jones, M., Davidson, A., Hibbert, L., Gruenwald, P., Schlaak, J., Ball, S., Foster, G.R., and Jacobs, M. 2005. Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression. J. Virol. 79, 5414–5420.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Jouannic, J.M., Friszer, S., Leparc-Goffart, I., Garel, C., and Eyrolle-Guignot, D. 2016. Zika virus infection in French Polynesia. Lancet 387, 1051–1052.PubMedCrossRefGoogle Scholar
  116. Junjhon, J., Edwards, T.J., Utaipat, U., Bowman, V.D., Holdaway, H.A., Zhang, W., Keelapang, P., Puttikhunt, C., Perera, R., Chipman, P.R., et al. 2010. Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles. J. Virol. 84, 8353–8358.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Kanai, R., Kar, K., Anthony, K., Gould, L.H., Ledizet, M., Fikrig, E., Marasco, W.A., Koski, R.A., and Modis, Y. 2006. Crystal structure of West Nile virus envelope glycoprotein reveals viral surface epitopes. J. Virol. 80, 11000–11008.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Kaufmann, B., Nybakken, G.E., Chipman, P.R., Zhang, W., Diamond, M.S., Fremont, D.H., Kuhn, R.J., and Rossmann, M.G. 2006. West Nile virus in complex with the Fab fragment of a neutralizing monoclonal antibody. Proc. Natl. Acad. Sci. USA 103, 12400–12404.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Kaufmann, B. and Rossmann, M.G. 2011. Molecular mechanisms involved in the early steps of flavivirus cell entry. Microbes Infect. 13, 1–9.PubMedCrossRefGoogle Scholar
  120. Kaufusi, P.H., Kelley, J.F., Yanagihara, R., and Nerurkar, V.R. 2014. Induction of endoplasmic reticulum-derived replication-competent membrane structures by West Nile virus non-structural protein 4B. PLoS One 9, e84040.CrossRefGoogle Scholar
  121. Khromykh, A.A., Meka, H., Guyatt, K.J., and Westaway, E.G. 2001. Essential role of cyclization sequences in flavivirus RNA replication. J. Virol. 75, 6719–6728.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Kim, J.K., Kim, J.M., Song, B.H., Yun, S.I., Yun, G.N., Byun, S.J., and Lee, Y.M. 2015. Profiling of viral proteins expressed from the genomic RNA of Japanese encephalitis virus using a panel of 15 region-specific polyclonal rabbit antisera: implications for viral gene expression. PLoS One 10, e0124318.Google Scholar
  123. Kindhauser, M.K., Allen, T., Frank, V., Santhana, R.S., and Dye, C. 2016. Zika: the origin and spread of a mosquito-borne virus. Bull. World Health Organ. 94, 675–686C.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Klema, V.J., Padmanabhan, R., and Choi, K.H. 2015. Flaviviral replication complex: coordination between RNA synthesis and 5’-RNA capping. Viruses 7, 4640–4656.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Kostyuchenko, V.A., Lim, E.X., Zhang, S., Fibriansah, G., Ng, T.S., Ooi, J.S., Shi, J., and Lok, S.M. 2016. Structure of the thermally stable Zika virus. Nature 533, 425–428.PubMedGoogle Scholar
  126. Kuhn, R.J., Zhang, W., Rossmann, M.G., Pletnev, S.V., Corver, J., Lenches, E., Jones, C.T., Mukhopadhyay, S., Chipman, P.R., Strauss, E.G., et al. 2002. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108, 717–725.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Kummerer, B.M. and Rice, C.M. 2002. Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles. J. Virol. 76, 4773–4784.PubMedPubMedCentralCrossRefGoogle Scholar
  128. Kuno, G. and Chang, G.J. 2007. Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch. Virol. 152, 687–696.PubMedCrossRefGoogle Scholar
  129. Kwong, J.C., Druce, J.D., and Leder, K. 2013. Zika virus infection acquired during brief travel to Indonesia. Am. J. Trop. Med. Hyg. 89, 516–517.PubMedPubMedCentralCrossRefGoogle Scholar
  130. Ladner, J.T., Wiley, M.R., Prieto, K., Yasuda, C.Y., Nagle, E., Kasper, M.R., Reyes, D., Vasilakis, N., Heang, V., Weaver, S.C., et al. 2016. Complete genome sequences of five Zika virus isolates. Genome Announc. 4, e00377-16.CrossRefGoogle Scholar
  131. Lanciotti, R.S., Kosoy, O.L., Laven, J.J., Velez, J.O., Lambert, A.J., Johnson, A.J., Stanfield, S.M., and Duffy, M.R. 2008. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg. Infect. Dis. 14, 1232–1239.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Lanciotti, R.S., Lambert, A.J., Holodniy, M., Saavedra, S., and Signor Ldel, C. 2016. Phylogeny of Zika virus in Western Hemisphere, 2015. Emerg. Infect. Dis. 22, 933–935.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Lednicky, J., Beau de Rochars, V.M., El Badry, M., Loeb, J., Telisma, T., Chavannes, S., Anilis, G., Cella, E., Ciccozzi, M., Rashid, M., et al. 2016. Zika virus outbreak in Haiti in 2014: molecular and clinical data. PLoS Negl. Trop. Dis. 10, e0004687.CrossRefGoogle Scholar
  134. Lee, J.W., Chu, J.J., and Ng, M.L. 2006. Quantifying the specific binding between West Nile virus envelope domain III protein and the cellular receptor aVb3 integrin. J. Biol. Chem. 281, 1352–1360.PubMedCrossRefGoogle Scholar
  135. Lee, E. and Lobigs, M. 2002. Mechanism of virulence attenuation of glycosaminoglycan-binding variants of Japanese encephalitis virus and Murray Valley encephalitis virus. J. Virol. 76, 4901–4911.PubMedPubMedCentralCrossRefGoogle Scholar
  136. Lei, J., Hansen, G., Nitsche, C., Klein, C.D., Zhang, L., and Hilgenfeld, R. 2016. Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor. Science 353, 503–505.PubMedCrossRefGoogle Scholar
  137. Lessler, J., Chaisson, L.H., Kucirka, L.M., Bi, Q., Grantz, K., Salje, H., Carcelen, A.C., Ott, C.T., Sheffield, J.S., Ferguson, N.M., et al. 2016. Assessing the global threat from Zika virus. Science 353, aaf8160.PubMedCrossRefGoogle Scholar
  138. Leung, J.Y., Pijlman, G.P., Kondratieva, N., Hyde, J., Mackenzie, J.M., and Khromykh, A.A. 2008. Role of nonstructural protein NS2A in flavivirus assembly. J. Virol. 82, 4731–4741.PubMedPubMedCentralCrossRefGoogle Scholar
  139. Li, L., Lok, S.M., Yu, I.M., Zhang, Y., Kuhn, R.J., Chen, J., and Rossmann, M.G. 2008. The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science 319, 1830–834.PubMedCrossRefGoogle Scholar
  140. Liao, M., Sanchez-San Martin, C., Zheng, A., and Kielian, M. 2010. In vitro reconstitution reveals key intermediate states of trimer formation by the dengue virus membrane fusion protein. J. Virol. 84, 5730–5740.PubMedPubMedCentralCrossRefGoogle Scholar
  141. Lin, C., Amberg, S.M., Chambers, T.J., and Rice, C.M. 1993. Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site. J. Virol. 67, 2327–2335.PubMedPubMedCentralGoogle Scholar
  142. Lin, K.C., Chang, H.L., and Chang, R.Y. 2004. Accumulation of a 3’-terminal genome fragment in Japanese encephalitis virus-infected mammalian and mosquito cells. J. Virol. 78, 5133–5138.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Lindenbach, B.D., Murray, C.L., Thiel, H.J., and Rice, C.M. 2013. Flaviviridae, pp. 712–746. In Knipe, D.M., Howley, P.M., Cohen, J.I., Griffin, D.E., Lamb, R.A., Martin, M.A., Racaniello, V.R., and Roizman, B. (eds.), Fields Virology. Wolters Kluwer Health, Philadelphia, Pennsylvania, USA.Google Scholar
  144. Liu, W.J., Chen, H.B., and Khromykh, A.A. 2003. Molecular and functional analyses of Kunjin virus infectious cDNA clones demonstrate the essential roles for NS2A in virus assembly and for a nonconservative residue in NS3 in RNA replication. J. Virol. 77, 7804–7813.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Liu, Z.Y., Li, X.F., Jiang, T., Deng, Y.Q., Zhao, H., Wang, H.J., Ye, Q., Zhu, S.Y., Qiu, Y., Zhou, X., et al. 2013. Novel cis-acting element within the capsid-coding region enhances flavivirus viral-NA replication by regulating genome cyclization. J. Virol. 87, 6804–6818.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Liu, Y., Liu, H., Zou, J., Zhang, B., and Yuan, Z. 2014. Dengue virus subgenomic RNA induces apoptosis through the Bcl-2-mediated PI3k/Akt signaling pathway. Virology 448, 15–25.PubMedCrossRefGoogle Scholar
  147. Liu, W.J., Wang, X.J., Mokhonov, V.V., Shi, P.Y., Randall, R., and Khromykh, A.A. 2005. Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins. J. Virol. 79, 1934–1942.PubMedPubMedCentralCrossRefGoogle Scholar
  148. Liu, L., Wu, W., Zhao, X., Xiong, Y., Zhang, S., Liu, X., Qu, J., Li, J., Nei, K., Liang, M., et al. 2016. Complete genome sequence of Zika virus from the first imported case in mainland China. Genome Announc. 4, e00291-16.Google Scholar
  149. Lobigs, M. 1993. Flavivirus premembrane protein cleavage and spike heterodimer secretion require the function of the viral proteinase NS3. Proc. Natl. Acad. Sci. USA 90, 6218–6222.PubMedPubMedCentralCrossRefGoogle Scholar
  150. Lodeiro, M.F., Filomatori, C.V., and Gamarnik, A.V. 2009. Structural and functional studies of the promoter element for dengue virus RNA replication. J. Virol. 83, 993–1008.PubMedCrossRefGoogle Scholar
  151. Lorenz, I.C., Allison, S.L., Heinz, F.X., and Helenius, A. 2002. Folding and dimerization of tick-borne encephalitis virus envelope proteins prM and E in the endoplasmic reticulum. J. Virol. 76, 5480–5491.PubMedPubMedCentralCrossRefGoogle Scholar
  152. Ma, L., Jones, C.T., Groesch, T.D., Kuhn, R.J., and Post, C.B. 2004. Solution structure of dengue virus capsid protein reveals another fold. Proc. Natl. Acad. Sci. USA 101, 3414–3419.PubMedPubMedCentralCrossRefGoogle Scholar
  153. Mackenzie, J.M., Khromykh, A.A., Jones, M.K., and Westaway, E.G. 1998. Subcellular localization and some biochemical properties of the flavivirus Kunjin nonstructural proteins NS2A and NS4A. Virology 245, 203–215.PubMedCrossRefGoogle Scholar
  154. Macnamara, F.N. 1954. Zika virus: a report on three cases of human infection during an epidemic of jaundice in Nigeria. Trans. R. Soc. Trop. Med. Hyg. 48, 139–145.PubMedCrossRefGoogle Scholar
  155. Manokaran, G., Finol, E., Wang, C., Gunaratne, J., Bahl, J., Ong, E.Z., Tan, H.C., Sessions, O.M., Ward, A.M., Gubler, D.J., et al. 2015. Dengue subgenomic RNA binds TRIM25 to inhibit interferon expression for epidemiological fitness. Science 350, 217–221.PubMedPubMedCentralCrossRefGoogle Scholar
  156. Mason, P.W., McAda, P.C., Dalrymple, J.M., Fournier, M.J., and Mason, T.L. 1987. Expression of Japanese encephalitis virus antigens in Escherichia coli. Virology 158, 361–372.PubMedCrossRefGoogle Scholar
  157. McLean, J.E., Wudzinska, A., Datan, E., Quaglino, D., and Zakeri, Z. 2011. Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. J. Biol. Chem. 286, 22147–22159.PubMedPubMedCentralCrossRefGoogle Scholar
  158. Melian, E.B., Hinzman, E., Nagasaki, T., Firth, A.E., Wills, N.M., Nouwens, A.S., Blitvich, B.J., Leung, J., Funk, A., Atkins, J.F., et al. 2010. NS1’ of flaviviruses in the Japanese encephalitis virus serogroup is a product of ribosomal frameshifting and plays a role in viral neuroinvasiveness. J. Virol. 84, 1641–1647.PubMedCrossRefGoogle Scholar
  159. Miller, S., Kastner, S., Krijnse-Locker, J., Buhler, S., and Bartenschlager, R. 2007. The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J. Biol. Chem. 282, 8873–8882.PubMedCrossRefGoogle Scholar
  160. Mlakar, J., Korva, M., Tul, N., Popovic, M., Poljsak-Prijatelj, M., Mraz, J., Kolenc, M., Resman Rus, K., Vesnaver Vipotnik, T., Fabjan Vodusek, V., et al. 2016. Zika virus associated with microcephaly. N. Engl. J. Med. 374, 951–958.PubMedCrossRefGoogle Scholar
  161. Modis, Y., Ogata, S., Clements, D., and Harrison, S.C. 2003. A ligandbinding pocket in the dengue virus envelope glycoprotein. Proc. Natl. Acad. Sci. USA 100, 6986–6991.PubMedPubMedCentralCrossRefGoogle Scholar
  162. Modis, Y., Ogata, S., Clements, D., and Harrison, S.C. 2004. Structure of the dengue virus envelope protein after membrane fusion. Nature 427, 313–319.PubMedCrossRefGoogle Scholar
  163. Monlun, E., Zeller, H., Le Guenno, B., Traore-Lamizana, M., Hervy, J.P., Adam, F., Ferrara, L., Fontenille, D., Sylla, R., and Mondo, M. 1993. Surveillance of the circulation of arbovirus of medical interest in the region of Eastern Senegal. Bull. Soc. Pathol. Exot. 86, 21–28.PubMedGoogle Scholar
  164. Moon, S.L., Anderson, J.R., Kumagai, Y., Wilusz, C.J., Akira, S., Khromykh, A.A., and Wilusz, J. 2012. A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability. RNA 18, 2029–2040.PubMedPubMedCentralCrossRefGoogle Scholar
  165. Moon, S.L., Dodd, B.J., Brackney, D.E., Wilusz, C.J., Ebel, G.D., and Wilusz, J. 2015. Flavivirus sfRNA suppresses antiviral RNA interference in cultured cells and mosquitoes and directly interacts with the RNAi machinery. Virology 485, 322–329.PubMedPubMedCentralCrossRefGoogle Scholar
  166. Moore, D.L., Causey, O.R., Carey, D.E., Reddy, S., Cooke, A.R., Akinkugbe, F.M., David-West, T.S., and Kemp, G.E. 1975. Arthropodborne viral infections of man in Nigeria, 1964-1970. Ann. Trop. Med. Parasitol. 69, 49–64.PubMedCrossRefGoogle Scholar
  167. Morrison, J., Aguirre, S., and Fernandez-Sesma, A. 2012. Innate immunity evasion by dengue virus. Viruses 4, 397–413.PubMedPubMedCentralCrossRefGoogle Scholar
  168. Mosso, C., Galvan-Mendoza, I.J., Ludert, J.E., and del Angel, R.M. 2008. Endocytic pathway followed by dengue virus to infect the mosquito cell line C6/36 HT. Virology 378, 193–199.PubMedCrossRefGoogle Scholar
  169. Mukhopadhyay, S., Kim, B.S., Chipman, P.R., Rossmann, M.G., and Kuhn, R.J. 2003. Structure of West Nile virus. Science 302, 248.PubMedCrossRefGoogle Scholar
  170. Munoz-Jordan, J.L., Laurent-Rolle, M., Ashour, J., Martinez-Sobrido, L., Ashok, M., Lipkin, W.I., and Garcia-Sastre, A. 2005. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J. Virol. 79, 8004–8013.PubMedPubMedCentralCrossRefGoogle Scholar
  171. Munoz-Jordan, J.L., Sanchez-Burgos, G.G., Laurent-Rolle, M., and Garcia-Sastre, A. 2003. Inhibition of interferon signaling by dengue virus. Proc. Natl. Acad. Sci. USA 100, 14333–14338.PubMedPubMedCentralCrossRefGoogle Scholar
  172. Musso, D., Cao-Lormeau, V.M., and Gubler, D.J. 2015. Zika virus: following the path of dengue and chikungunya? Lancet 386, 243–244.Google Scholar
  173. Musso, D. and Gubler, D.J. 2016. Zika virus. Clin. Microbiol. Rev. 29, 487–524.PubMedCrossRefGoogle Scholar
  174. Musso, D., Nilles, E.J., and Cao-Lormeau, V.M. 2014. Rapid spread of emerging Zika virus in the Pacific area. Clin. Microbiol. Infect. 20, O595–596.PubMedCrossRefGoogle Scholar
  175. Navarro-Sanchez, E., Altmeyer, R., Amara, A., Schwartz, O., Fieschi, F., Virelizier, J.L., Arenzana-Seisdedos, F., and Despres, P. 2003. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquitocell-derived dengue viruses. EMBO Rep. 4, 723–728.PubMedPubMedCentralCrossRefGoogle Scholar
  176. Nayak, V., Dessau, M., Kucera, K., Anthony, K., Ledizet, M., and Modis, Y. 2009. Crystal structure of dengue virus type 1 envelope protein in the postfusion conformation and its implications for membrane fusion. J. Virol. 83, 4338–4344.PubMedPubMedCentralCrossRefGoogle Scholar
  177. Nybakken, G.E., Nelson, C.A., Chen, B.R., Diamond, M.S., and Fremont, D.H. 2006. Crystal structure of the West Nile virus envelope glycoprotein. J. Virol. 80, 11467–11474.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Oehler, E., Watrin, L., Larre, P., Leparc-Goffart, I., Lastere, S., Valour, F., Baudouin, L., Mallet, H., Musso, D., and Ghawche, F. 2014. Zika virus infection complicated by Guillain-Barré syndrome–case report, French Polynesia, December 2013. Euro Surveill. 19, 20720.PubMedCrossRefGoogle Scholar
  179. Olson, J.G., Ksiazek, T.G., Gubler, D.J., Lubis, S.I., Simanjuntak, G., Lee, V.H., Nalim, S., Juslis, K., and See, R. 1983. A survey for arboviral antibodies in sera of humans and animals in Lombok, Republic of Indonesia. Ann. Trop. Med. Parasitol. 77, 131–137.PubMedCrossRefGoogle Scholar
  180. Olson, J.G., Ksiazek, T.G., Suhandiman, and Triwibowo. 1981. Zika virus, a cause of fever in Central Java, Indonesia. Trans. R. Soc. Trop. Med. Hyg. 75, 389–393.PubMedCrossRefGoogle Scholar
  181. Olsthoorn, R.C. and Bol, J.F. 2001. Sequence comparison and secondary structure analysis of the 3’ noncoding region of flavivirus genomes reveals multiple pseudoknots. RNA 7, 1370–1377.PubMedPubMedCentralGoogle Scholar
  182. PAHO/WHO. 2016. Zika suspected and confirmed cases reported by countries and territories in the Americas (Cumulative cases), 2015-2016. Pan American Health Organization/World Health Organization, Washington, D.C. November 17, 2016. &Itemid=270&gid=36937&lang=en.Google Scholar
  183. PAHO/WHO. 2017. Zika -epidemiological update. Pan American Health Organization/World Health Organization, Washington, D.C. January 12, 2017. 37671&lang=en.Google Scholar
  184. Paranjape, S.M. and Harris, E. 2010. Control of dengue virus translation and replication. Curr. Top. Microbiol. Immunol. 338, 15–34.PubMedGoogle Scholar
  185. Patkar, C.G. and Kuhn, R.J. 2008. Yellow fever virus NS3 plays an essential role in virus assembly independent of its known enzymatic functions. J. Virol. 82, 3342–3352.PubMedPubMedCentralCrossRefGoogle Scholar
  186. Perera-Lecoin, M., Meertens, L., Carnec, X., and Amara, A. 2013. Flavivirus entry receptors: an update. Viruses 6, 69–88.PubMedPubMedCentralCrossRefGoogle Scholar
  187. Perkasa, A., Yudhaputri, F., Haryanto, S., Hayati, R.F., Ma’roef, C.N., Antonjaya, U., Yohan, B., Myint, K.S., Ledermann, J.P., Rosenberg, R., et al. 2016. Isolation of Zika virus from febrile patient, Indonesia. Emerg. Infect. Dis. 22, 924–925.PubMedPubMedCentralCrossRefGoogle Scholar
  188. Phoo, W.W., Li, Y., Zhang, Z., Lee, M.Y., Loh, Y.R., Tan, Y.B., Ng, E.Y., Lescar, J., Kang, C., and Luo, D. 2016. Structure of the NS2BNS3 protease from Zika virus after self-cleavage. Nat. Commun. 7, 13410.PubMedPubMedCentralCrossRefGoogle Scholar
  189. Pierson, T.C. and Diamond, M.S. 2012. Degrees of maturity: the complex structure and biology of flaviviruses. Curr. Opin. Virol. 2, 168–175.PubMedPubMedCentralCrossRefGoogle Scholar
  190. Pierson, T.C. and Kielian, M. 2013. Flaviviruses: braking the entering. Curr. Opin. Virol. 3, 3–12.PubMedPubMedCentralCrossRefGoogle Scholar
  191. Pijlman, G.P. 2014. Flavivirus RNAi suppression: decoding noncoding RNA. Curr. Opin. Virol. 7, 55–60.PubMedCrossRefGoogle Scholar
  192. Pijlman, G.P., Funk, A., Kondratieva, N., Leung, J., Torres, S., van der Aa, L., Liu, W.J., Palmenberg, A.C., Shi, P.Y., Hall, R.A., et al. 2008. A highly structured, nuclease-resistant, noncoding RNA produced by flaviviruses is required for pathogenicity. Cell Host Microbe 4, 579–591.PubMedCrossRefGoogle Scholar
  193. Pijlman, G.P., Kondratieva, N., and Khromykh, A.A. 2006. Translation of the flavivirus Kunjin NS3 gene in cis but not its RNA sequence or secondary structure is essential for efficient RNA packaging. J. Virol. 80, 11255–11264.PubMedPubMedCentralCrossRefGoogle Scholar
  194. Pokidysheva, E., Zhang, Y., Battisti, A.J., Bator-Kelly, C.M., Chipman, P.R., Xiao, C., Gregorio, G.G., Hendrickson, W.A., Kuhn, R.J., and Rossmann, M.G. 2006. Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN. Cell 124, 485–493.PubMedCrossRefGoogle Scholar
  195. Pond, W.L. 1963. Arthropod-borne virus antibodies in sera from residents of South-East Asia. Trans. R. Soc. Trop. Med. Hyg. 57, 364–371.PubMedCrossRefGoogle Scholar
  196. Preugschat, F. and Strauss, J.H. 1991. Processing of nonstructural proteins NS4A and NS4B of dengue 2 virus in vitro and in vivo. Virology 185, 689–697.PubMedCrossRefGoogle Scholar
  197. Ray, D., Shah, A., Tilgner, M., Guo, Y., Zhao, Y., Dong, H., Deas, T.S., Zhou, Y., Li, H., and Shi, P.Y. 2006. West Nile virus 5’-cap structure is formed by sequential guanine N-7 and ribose 2’-O methylations by nonstructural protein 5. J. Virol. 80, 8362–8370.PubMedPubMedCentralCrossRefGoogle Scholar
  198. Rey, F.A., Heinz, F.X., Mandl, C., Kunz, C., and Harrison, S.C. 1995. The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolution. Nature 375, 291–298.PubMedCrossRefGoogle Scholar
  199. Rice, C.M., Lenches, E.M., Eddy, S.R., Shin, S.J., Sheets, R.L., and Strauss, J.H. 1985. Nucleotide sequence of yellow fever virus: implications for flavivirus gene expression and evolution. Science 229, 726–733.PubMedCrossRefGoogle Scholar
  200. Robin, Y. and Mouchet, J. 1975. Serological and entomological study on yellow fever in Sierra Leone. Bull. Soc. Pathol. Exot. Filiales 68, 249–258.PubMedGoogle Scholar
  201. Roby, J.A., Pijlman, G.P., Wilusz, J., and Khromykh, A.A. 2014. Noncoding subgenomic flavivirus RNA: multiple functions in West Nile virus pathogenesis and modulation of host responses. Viruses 6, 404–427.PubMedPubMedCentralCrossRefGoogle Scholar
  202. Roosendaal, J., Westaway, E.G., Khromykh, A., and Mackenzie, J.M. 2006. Regulated cleavages at the West Nile virus NS4A-2K-NS4B junctions play a major role in rearranging cytoplasmic membranes and Golgi trafficking of the NS4A protein. J. Virol. 80, 4623–4632.PubMedPubMedCentralCrossRefGoogle Scholar
  203. Roth, A., Mercier, A., Lepers, C., Hoy, D., Duituturaga, S., Benyon, E., Guillaumot, L., and Souares, Y. 2014. Concurrent outbreaks of dengue, chikungunya and Zika virus infections–an unprecedented epidemic wave of mosquito-borne viruses in the Pacific 2012–2014. Euro Surveill. 19, 20929.PubMedCrossRefGoogle Scholar
  204. Saluzzo, J.F., Gonzalez, J.P., Herve, J.P., and Georges, A.J. 1981. Serological survey for the prevalence of certain arboviruses in the human population of the south-east area of Central African Republic. Bull. Soc. Pathol. Exot. Filiales 74, 490–499.PubMedGoogle Scholar
  205. Saluzzo, J.F., Ivanoff, B., Languillat, G., and Georges, A.J. 1982. Serological survey for arbovirus antibodies in the human and simian populations of the South-East of Gabon. Bull. Soc. Pathol. Exot. Filiales 75, 262–266.PubMedGoogle Scholar
  206. Schnettler, E., Sterken, M.G., Leung, J.Y., Metz, S.W., Geertsema, C., Goldbach, R.W., Vlak, J.M., Kohl, A., Khromykh, A.A., and Pijlman, G.P. 2012. Noncoding flavivirus RNA displays RNA interference suppressor activity in insect and mammalian cells. J. Virol. 86, 13486–13500.PubMedPubMedCentralCrossRefGoogle Scholar
  207. Schuessler, A., Funk, A., Lazear, H.M., Cooper, D.A., Torres, S., Daffis, S., Jha, B.K., Kumagai, Y., Takeuchi, O., Hertzog, P., et al. 2012. West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response. J. Virol. 86, 5708–5718.PubMedPubMedCentralCrossRefGoogle Scholar
  208. Schuler-Faccini, L., Ribeiro, E.M., Feitosa, I.M., Horovitz, D.D., Cavalcanti, D.P., Pessoa, A., Doriqui, M.J., Neri, J.I., Neto, J.M., Wanderley, H.Y., et al. 2016. Possible association between Zika virus infection and microcephaly–Brazil, 2015. MMWR Morb. Mortal. Wkly. Rep. 65, 59–62.PubMedCrossRefGoogle Scholar
  209. Selisko, B., Wang, C., Harris, E., and Canard, B. 2014. Regulation of Flavivirus RNA synthesis and replication. Curr. Opin. Virol. 9, 74–83.PubMedCrossRefGoogle Scholar
  210. Silva, P.A., Pereira, C.F., Dalebout, T.J., Spaan, W.J., and Bredenbeek, P.J. 2010. An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1. J. Virol. 84, 11395–11406.PubMedPubMedCentralCrossRefGoogle Scholar
  211. Simmonds, P., Becher, B., Bukh, J., Gould, E.A., Meyers, G., Monath, T., Muerhoff, S., Pletnev, A., Rico-Hesse, R., Smith, D.B., Stapleton, J.T., and ICTV Report Consortium. 2017. ICTV virus taxonomy profiles: Flaviviridae. J. Gen. Virol. In Press.Google Scholar
  212. Simpson, D.I. 1964. Zika virus infection in man. Trans. R. Soc. Trop. Med. Hyg. 58, 335–338.PubMedCrossRefGoogle Scholar
  213. Sirohi, D., Chen, Z., Sun, L., Klose, T., Pierson, T.C., Rossmann, M.G., and Kuhn, R.J. 2016. The 3.8 Å resolution cryo-EM structure of Zika virus. Science 352, 467–470.PubMedPubMedCentralCrossRefGoogle Scholar
  214. Smithburn, K.C. 1952. Neutralizing antibodies against certain recently isolated viruses in the sera of human beings residing in East Africa. J. Immunol. 69, 223–234.PubMedGoogle Scholar
  215. Smithburn, K.C. 1954. Neutralizing antibodies against arthropodborne viruses in the sera of long-time residents of Malaya and Borneo. Am. J. Hyg. 59, 157–163.PubMedGoogle Scholar
  216. Smithburn, K.C., Kerr, J.A., and Gatne, P.B. 1954a. Neutralizing antibodies against certain viruses in the sera of residents of India. J. Immunol. 72, 248–257.PubMedGoogle Scholar
  217. Smithburn, K.C., Taylor, R.M., Rizk, F., and Kader, A. 1954b. Immunity to certain arthropod-borne viruses among indigenous residents of Egypt. Am. J. Trop. Med. Hyg. 3, 9–18.PubMedGoogle Scholar
  218. Song, H., Qi, J., Haywood, J., Shi, Y., and Gao, G.F. 2016. Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses. Nat. Struct. Mol. Biol. 23, 456–458.PubMedCrossRefGoogle Scholar
  219. Song, B.H., Yun, S.I., Choi, Y.J., Kim, J.M., Lee, C.H., and Lee, Y.M. 2008. A complex RNA motif defined by three discontinuous 5-nucleotide-long strands is essential for Flavivirus RNA replication. RNA 14, 1791–1813.PubMedPubMedCentralCrossRefGoogle Scholar
  220. Speight, G., Coia, G., Parker, M.D., and Westaway, E.G. 1988. Gene mapping and positive identification of the non-structural proteins NS2A, NS2B, NS3, NS4B and NS5 of the flavivirus Kunjin and their cleavage sites. J. Gen. Virol. 69, 23–34.PubMedCrossRefGoogle Scholar
  221. Stadler, K., Allison, S.L., Schalich, J., and Heinz, F.X. 1997. Proteolytic activation of tick-borne encephalitis virus by furin. J. Virol. 71, 8475–8481.PubMedPubMedCentralGoogle Scholar
  222. Stettler, K., Beltramello, M., Espinosa, D.A., Graham, V., Cassotta, A., Bianchi, S., Vanzetta, F., Minola, A., Jaconi, S., Mele, F., et al. 2016. Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection. Science 353, 823–826.PubMedCrossRefGoogle Scholar
  223. Stiasny, K., Allison, S.L., Marchler-Bauer, A., Kunz, C., and Heinz, F.X. 1996. Structural requirements for low-pH-induced rearrangements in the envelope glycoprotein of tick-borne encephalitis virus. J. Virol. 70, 8142–8147.PubMedPubMedCentralGoogle Scholar
  224. Stiasny, K., Allison, S.L., Schalich, J., and Heinz, F.X. 2002. Membrane interactions of the tick-borne encephalitis virus fusion protein E at low pH. J. Virol. 76, 3784–3790.PubMedPubMedCentralCrossRefGoogle Scholar
  225. Stiasny, K., Bressanelli, S., Lepault, J., Rey, F.A., and Heinz, F.X. 2004. Characterization of a membrane-associated trimeric lowpH-induced form of the class IIviral fusion protein E from tickborne encephalitis virus and its crystallization. J. Virol. 78, 3178–3183.PubMedPubMedCentralCrossRefGoogle Scholar
  226. Stiasny, K., Fritz, R., Pangerl, K., and Heinz, F.X. 2011. Molecular mechanisms of flavivirus membrane fusion. Amino Acids 41, 1159–1163.PubMedCrossRefGoogle Scholar
  227. Stiasny, K., Kossl, C., Lepault, J., Rey, F.A., and Heinz, F.X. 2007. Characterization of a structural intermediate of flavivirus membrane fusion. PLoS Pathog. 3, e20.CrossRefGoogle Scholar
  228. Stocks, C.E. and Lobigs, M. 1998. Signal peptidase cleavage at the flavivirus C-prM junction: dependence on the viral NS2B-3 protease for efficient processing requires determinants in C, the signal peptide, and prM. J. Virol. 72, 2141–2149.PubMedPubMedCentralGoogle Scholar
  229. Tappe, D., Nachtigall, S., Kapaun, A., Schnitzler, P., Gunther, S., and Schmidt-Chanasit, J. 2015. Acute Zika virus infection after travel to Malaysian Borneo, September 2014. Emerg. Infect. Dis. 21, 911–913.PubMedPubMedCentralCrossRefGoogle Scholar
  230. Tappe, D., Rissland, J., Gabriel, M., Emmerich, P., Gunther, S., Held, G., Smola, S., and Schmidt-Chanasit, J. 2014. First case of laboratory-confirmed Zika virus infection imported into Europe, November 2013. Euro Surveill. 19, 20685.PubMedCrossRefGoogle Scholar
  231. Tassaneetrithep, B., Burgess, T.H., Granelli-Piperno, A., Trumpfheller, C., Finke, J., Sun, W., Eller, M.A., Pattanapanyasat, K., Sarasombath, S., Birx, D.L., et al. 2003. DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J. Exp. Med. 197, 823–829.PubMedPubMedCentralCrossRefGoogle Scholar
  232. Thurner, C., Witwer, C., Hofacker, I.L., and Stadler, P.F. 2004. Conserved RNA secondary structures in Flaviviridae genomes. J. Gen. Virol. 85, 1113–1124.PubMedCrossRefGoogle Scholar
  233. Tilgner, M. and Shi, P.Y. 2004. Structure and function of the 3’ terminal six nucleotides of the West Nile virus genome in viral replication. J. Virol. 78, 8159–8171.PubMedPubMedCentralCrossRefGoogle Scholar
  234. Tognarelli, J., Ulloa, S., Villagra, E., Lagos, J., Aguayo, C., Fasce, R., Parra, B., Mora, J., Becerra, N., Lagos, N., et al. 2016. A report on the outbreak of Zika virus on Easter Island, South Pacific, 2014. Arch. Virol. 161, 665–668.PubMedCrossRefGoogle Scholar
  235. van der Schaar, H.M., Rust, M.J., Chen, C., van der Ende-Metselaar, H., Wilschut, J., Zhuang, X., and Smit, J.M. 2008. Dissecting the cell entry pathway of dengue virus by single-particle tracking in living cells. PLoS Pathog. 4, e1000244.CrossRefGoogle Scholar
  236. van der Schaar, H.M., Rust, M.J., Waarts, B.L., van der Ende-Metselaar, H., Kuhn, R.J., Wilschut, J., Zhuang, X., and Smit, J.M. 2007. Characterization of the early events in dengue virus cell entry by biochemical assays and single-virus tracking. J. Virol. 81, 12019–12028.PubMedPubMedCentralCrossRefGoogle Scholar
  237. Vashist, S., Anantpadma, M., Sharma, H., and Vrati, S. 2009. La protein binds the predicted loop structures in the 3’ non-coding region of Japanese encephalitis virus genome: role in virus replication. J. Gen. Virol. 90, 1343–1352.PubMedCrossRefGoogle Scholar
  238. Victora, C.G., Schuler-Faccini, L., Matijasevich, A., Ribeiro, E., Pessoa, A., and Barros, F.C. 2016. Microcephaly in Brazil: how to interpret reported numbers? Lancet 387, 621–624.Google Scholar
  239. Villordo, S.M., Alvarez, D.E., and Gamarnik, A.V. 2010. A balance between circular and linear forms of the dengue virus genome is crucial for viral replication. RNA 16, 2325–2335.PubMedPubMedCentralCrossRefGoogle Scholar
  240. Villordo, S.M., Carballeda, J.M., Filomatori, C.V., and Gamarnik, A.V. 2016. RNA structure duplications and flavivirus host adaptation. Trends Microbiol. 24, 270–283.PubMedCrossRefGoogle Scholar
  241. Villordo, S.M., Filomatori, C.V., Sanchez-Vargas, I., Blair, C.D., and Gamarnik, A.V. 2015. Dengue virus RNA structure specialization facilitates host adaptation. PLoS Pathog. 11, e1004604.CrossRefGoogle Scholar
  242. Wang, L., Valderramos, S.G., Wu, A., Ouyang, S., Li, C., Brasil, P., Bonaldo, M., Coates, T., Nielsen-Saines, K., Jiang, T., et al. 2016. From mosquitos to humans: genetic evolution of Zika virus. Cell Host Microbe 19, 561–565.PubMedCrossRefGoogle Scholar
  243. Watrin, L., Ghawche, F., Larre, P., Neau, J.P., Mathis, S., and Fournier, E. 2016. Guillain-Barré syndrome (42 cases) occurring during a Zika virus outbreak in French Polynesia. Medicine (Baltimore) 95, e3257.CrossRefGoogle Scholar
  244. Welsch, S., Miller, S., Romero-Brey, I., Merz, A., Bleck, C.K., Walther, P., Fuller, S.D., Antony, C., Krijnse-Locker, J., and Bartenschlager, R. 2009. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5, 365–375.PubMedCrossRefGoogle Scholar
  245. Wengler, G., Castle, E., Leidner, U., Nowak, T., and Wengler, G. 1985. Sequence analysis of the membrane protein V3 of the flavivirus West Nile virus and of its gene. Virology 147, 264–274.PubMedCrossRefGoogle Scholar
  246. Westaway, E.G., Mackenzie, J.M., Kenney, M.T., Jones, M.K., and Khromykh, A.A. 1997. Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures. J. Virol. 71, 6650–6661.PubMedPubMedCentralGoogle Scholar
  247. WHO. 2015. Zika virus outbreaks in the Americas. Wkly. Epidemiol. Rec. 90, 609–610.Google Scholar
  248. WHO. 2016a. WHO statement on the first meeting of the International Health Regulations 2005 (IHR 2005) Emergency Committee on Zika virus and observed increase in neurological disorders and neonatal malformations. World Health Organization, Geneva, Switzerland. February 1, 2016. mediacentre/news/statements/2016/1st-emergency-committeezika/ en/.Google Scholar
  249. WHO. 2016b. WHO statement: fifth meeting of the Emergency Committee under the International Health Regulations (2005) regarding microcephaly, other neurological disorders and Zika virus. World Health Organization, Geneva, Switzerland. November 18, 2016. 2016/zika-fifth-ec/en/.Google Scholar
  250. Wu, R.H., Tsai, M.H., Chao, D.Y., and Yueh, A. 2015. Scanning mutagenesis studies reveal a potential intramolecular interaction within the C-terminal half of dengue virus NS2A involved in viral RNA replication and virus assembly and secretion. J. Virol. 89, 4281–4295.PubMedPubMedCentralCrossRefGoogle Scholar
  251. Wu, K.P., Wu, C.W., Tsao, Y.P., Kuo, T.W., Lou, Y.C., Lin, C.W., Wu, S.C., and Cheng, J.W. 2003. Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein. J. Biol. Chem. 278, 46007–46013.PubMedCrossRefGoogle Scholar
  252. Xie, X., Zou, J., Puttikhunt, C., Yuan, Z., and Shi, P.Y. 2015. Two distinct sets of NS2A molecules are responsible for dengue virus RNA synthesis and virion assembly. J. Virol. 89, 1298–1313.PubMedCrossRefGoogle Scholar
  253. Xu, X., Song, H., Qi, J., Liu, Y., Wang, H., Su, C., Shi, Y., and Gao, G.F. 2016. Contribution of intertwined loop to membrane association revealed by Zika virus full-length NS1 structure. EMBO J. 35, 2170–2178.PubMedPubMedCentralCrossRefGoogle Scholar
  254. Yamshchikov, V.F. and Compans, R.W. 1994. Processing of the intracellular form of the West Nile virus capsid protein by the viral NS2B-NS3 protease: an in vitro study. J. Virol. 68, 5765–5771.PubMedPubMedCentralGoogle Scholar
  255. Ye, Q., Li, X.F., Zhao, H., Li, S.H., Deng, Y.Q., Cao, R.Y., Song, K.Y., Wang, H.J., Hua, R.H., Yu, Y.X., et al. 2012. A single nucleotide mutation in NS2A of Japanese encephalitis-live vaccine virus (SA14-14-2) ablates NS1’ formation and contributes to attenuation. J. Gen. Virol. 93, 1959–1964.PubMedCrossRefGoogle Scholar
  256. Yocupicio-Monroy, M., Padmanabhan, R., Medina, F., and del Angel, R.M. 2007. Mosquito La protein binds to the 3’ untranslated region of the positive and negative polarity dengue virus RNAs and relocates to the cytoplasm of infected cells. Virology 357, 29–40.PubMedCrossRefGoogle Scholar
  257. Yu, I.M., Holdaway, H.A., Chipman, P.R., Kuhn, R.J., Rossmann, M.G., and Chen, J. 2009. Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion. J. Virol. 83, 12101–12107.PubMedPubMedCentralCrossRefGoogle Scholar
  258. Yu, L. and Markoff, L. 2005. The topology of bulges in the long stem of the flavivirus 3’ stem-loop is a major determinant of RNA replication competence. J. Virol. 79, 2309–2324.PubMedPubMedCentralCrossRefGoogle Scholar
  259. Yu, I.M., Zhang, W., Holdaway, H.A., Li, L., Kostyuchenko, V.A., Chipman, P.R., Kuhn, R.J., Rossmann, M.G., and Chen, J. 2008. Structure of the immature dengue virus at low pH primes proteolytic maturation. Science 319, 1834–1837.PubMedCrossRefGoogle Scholar
  260. Yun, S.I., Choi, Y.J., Song, B.H., and Lee, Y.M. 2009. 3’ cis-acting elements that contribute to the competence and efficiency of Japanese encephalitis virus genome replication: functional importance of sequence duplications, deletions, and substitutions. J. Virol. 83, 7909–7930.PubMedPubMedCentralCrossRefGoogle Scholar
  261. Yun, S.I. and Lee, Y.M. 2006. Japanese encephalitis virus: molecular biology and vaccine development, pp. 225–271. In Kalitzky, M. and Borowski, P. (eds.), Molecular biology of the flavivirus. Horizon Scientific Press, Norwich, UK.Google Scholar
  262. Yun, S.I., Song, B.H., Frank, J.C., Julander, J.G., Polejaeva, I.A., Davies, C.J., White, K.L., and Lee, Y.M. 2016a. Complete genome sequences of three historically important, spatiotemporally distinct, and genetically divergent strains of Zika virus: MR-766, P6-740, and PRVABC-59. Genome Announc. 4, e00800-16.Google Scholar
  263. Yun, S.I., Song, B.H., Polejaeva, I.A., Davies, C.J., White, K.L., and Lee, Y.M. 2016b. Comparison of the live-attenuated Japanese encephalitis vaccine SA14-14-2 strain with its pre-attenuated virulent parent SA14 strain: similarities and differences in vitro and in vivo. J. Gen. Virol. 97, 2575–2591.PubMedCrossRefGoogle Scholar
  264. Zammarchi, L., Tappe, D., Fortuna, C., Remoli, M.E., Gunther, S., Venturi, G., Bartoloni, A., and Schmidt-Chanasit, J. 2015. Zika virus infection in a traveller returning to Europe from Brazil, March 2015. Euro Surveill. 20, 21153.PubMedCrossRefGoogle Scholar
  265. Zanluca, C., Melo, V.C., Mosimann, A.L., Santos, G.I., Santos, C.N., and Luz, K. 2015. First report of autochthonous transmission of Zika virus in Brazil. Mem. Inst. Oswaldo Cruz 110, 569–572.PubMedPubMedCentralCrossRefGoogle Scholar
  266. Zeng, L., Falgout, B., and Markoff, L. 1998. Identification of specific nucleotide sequences within the conserved 3’-SL in the dengue type 2 virus genome required for replication. J. Virol. 72, 7510–7522.PubMedPubMedCentralGoogle Scholar
  267. Zhang, W., Chipman, P.R., Corver, J., Johnson, P.R., Zhang, Y., Mukhopadhyay, S., Baker, T.S., Strauss, J.H., Rossmann, M.G., and Kuhn, R.J. 2003a. Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat. Struct. Biol. 10, 907–912.PubMedPubMedCentralCrossRefGoogle Scholar
  268. Zhang, Y., Corver, J., Chipman, P.R., Zhang, W., Pletnev, S.V., Sedlak, D., Baker, T.S., Strauss, J.H., Kuhn, R.J., and Rossmann, M.G. 2003b. Structures of immature flavivirus particles. EMBO J. 22, 2604–2613.PubMedPubMedCentralCrossRefGoogle Scholar
  269. Zhang, B., Dong, H., Stein, D.A., Iversen, P.L., and Shi, P.Y. 2008. West Nile virus genome cyclization and RNA replication require two pairs of long-distance RNA interactions. Virology 373, 1–13.PubMedCrossRefGoogle Scholar
  270. Zhang, C., Feng, T., Cheng, J., Li, Y., Yin, X., Zeng, W., Jin, X., Li, Y., Guo, F., and Jin, T. 2016a. Structure of the NS5 methyltransferase from Zika virus and implications in inhibitor design. Biochem. Biophys. Res. Commun. pii: S0006-291X(16)31963-5.Google Scholar
  271. Zhang, X., Ge, P., Yu, X., Brannan, J.M., Bi, G., Zhang, Q., Schein, S., and Zhou, Z.H. 2013b. Cryo-EM structure of the mature dengue virus at 3.5-Å resolution. Nat. Struct. Mol. Biol. 20, 105–110.PubMedCrossRefGoogle Scholar
  272. Zhang, W., Kaufmann, B., Chipman, P.R., Kuhn, R.J., and Rossmann, M.G. 2013a. Membrane curvature in flaviviruses. J. Struct. Biol. 183, 86–94.PubMedPubMedCentralCrossRefGoogle Scholar
  273. Zhang, Y., Kaufmann, B., Chipman, P.R., Kuhn, R.J., and Rossmann, M.G. 2007. Structure of immature West Nile virus. J. Virol. 81, 6141–6145.PubMedPubMedCentralCrossRefGoogle Scholar
  274. Zhang, Z., Li, Y., Loh, Y.R., Phoo, W.W., Hung, A.W., Kang, C., and Luo, D. 2016b. Crystal structure of unlinked NS2B-NS3 protease from Zika virus. Science 354, 1597–1600.PubMedCrossRefGoogle Scholar
  275. Zhang, Y., Zhang, W., Ogata, S., Clements, D., Strauss, J.H., Baker, T.S., Kuhn, R.J., and Rossmann, M.G. 2004. Conformational changes of the flavivirus E glycoprotein. Structure 12, 1607–1618.PubMedPubMedCentralCrossRefGoogle Scholar
  276. Zhu, Z., Chan, J.F., Tee, K.M., Choi, G.K., Lau, S.K., Woo, P.C., Tse, H., and Yuen, K.Y. 2016. Comparative genomic analysis of preepidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic. Emerg. Microbes Infect. 5, e22.CrossRefGoogle Scholar
  277. Zuker, M. 2003. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406–3415.PubMedPubMedCentralCrossRefGoogle Scholar
  278. Zust, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B.W., Ziebuhr, J., Szretter, K.J., Baker, S.C., Barchet, W., Diamond, M.S., et al. 2011. Ribose 2’-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat. Immunol. 12, 137–143.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Animal, Dairy, and Veterinary SciencesUtah State UniversityLoganUSA
  2. 2.Utah Science Technology and Research, College of Agriculture and Applied SciencesUtah State UniversityLoganUSA

Personalised recommendations