Abstract
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.
Article PDF
Similar content being viewed by others
References
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.
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.
Adiga, R. 2016. Phylogenetic analysis of the NS5 gene of Zika virus. J. Med. Virol. 88, 1821–1826.
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.
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.
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.
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.
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.
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.
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.
Apte-Sengupta, S., Sirohi, D., and Kuhn, R.J. 2014. Coupling of replication and assembly in flaviviruses. Curr. Opin. Virol. 9, 134–142.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Brinton, M.A. 2013. Replication cycle and molecular biology of the West Nile virus. Viruses 6, 13–53.
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.
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.
Campos, G.S., Bandeira, A.C., and Sardi, S.I. 2015. Zika virus outbreak, Bahia, Brazil. Emerg. Infect. Dis. 21, 1885–1886.
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.
Cao-Lormeau, V.M. and Musso, D. 2014. Emerging arboviruses in the Pacific. Lancet 384, 1571–1572.
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.
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.
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.
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.
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.
CDC. 2016. All countries and territories with active Zika virus transmission. Centers for Disease Control and Prevention, Atlanta, Georgia. December 16, 2016. https://www.cdc.gov/zika/geo/activecountries. html.
CDC. 2017a. Case counts in the US. Centers for Disease Control and Prevention, Atlanta, Georgia. January 19, 2017. https://www. cdc.gov/zika/geo/united-states.html.
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. http://www.cdc.gov/zika/geo/pregnancy-outcomes.html.
CDC. 2017c. Zika cases reported in the United States. Centers for Disease Control and Prevention, Atlanta, Georgia. January 19, 2017. https://www.cdc.gov/zika/intheus/maps-zika-us.html.
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.
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.
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.
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.
Charley, P.A. and Wilusz, J. 2016. Standing your ground to exoribonucleases: function of Flavivirus long non-coding RNAs. Virus Res. 212, 70–77.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dong, H., Zhang, B., and Shi, P.Y. 2008a. Flavivirus methyltransferase: a novel antiviral target. Antiviral Res. 80, 1–10.
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.
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.
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.
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.
ECDC. 2017. Current Zika transmission. European Centre for Disease Prevention and Control, Stockholm, Sweden. January 20, 2017. http://ecdc.europa.eu/en/healthtopics/zika_virus_infection/zikaoutbreak/ pages/zika-countries-with-transmission.aspx.
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.
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.
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.
Fagbami, A. 1977. Epidemiological investigations on arbovirus infections at Igbo-Ora, Nigeria. Trop. Geogr. Med. 29, 187–191.
Fagbami, A.H. 1979. Zika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo State. J. Hyg. 83, 213–219.
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.
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.
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.
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.
Fauci, A.S. and Morens, D.M. 2016. Zika virus in the Americas–yet another arbovirus threat. N. Engl. J. Med. 374, 601–604.
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.
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.
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.
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.
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.
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.
Gebhard, L.G., Filomatori, C.V., and Gamarnik, A.V. 2011. Functional RNA elements in the dengue virus genome. Viruses 3, 1739–1756.
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.
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.
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.
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.
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.
Gould, E.A. and Solomon, T. 2008. Pathogenic flaviviruses. Lancet 371, 500–509.
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.
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.
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.
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.
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.
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.
Harrison, S.C. 2015. Viral membrane fusion. Virology 479-480, 498–507.
Hayes, E.B. 2009. Zika virus outside Africa. Emerg. Infect. Dis. 15, 1347–1350.
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.
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.
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.
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.
Iglesias, N.G. and Gamarnik, A.V. 2011. Dynamic RNA structures in the dengue virus genome. RNA Biol. 8, 249–257.
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.
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.
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.
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.
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.
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.
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.
Kaufmann, B. and Rossmann, M.G. 2011. Molecular mechanisms involved in the early steps of flavivirus cell entry. Microbes Infect. 13, 1–9.
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.
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.
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.
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.
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.
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.
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.
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.
Kuno, G. and Chang, G.J. 2007. Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch. Virol. 152, 687–696.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Morrison, J., Aguirre, S., and Fernandez-Sesma, A. 2012. Innate immunity evasion by dengue virus. Viruses 4, 397–413.
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.
Mukhopadhyay, S., Kim, B.S., Chipman, P.R., Rossmann, M.G., and Kuhn, R.J. 2003. Structure of West Nile virus. Science 302, 248.
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.
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.
Musso, D., Cao-Lormeau, V.M., and Gubler, D.J. 2015. Zika virus: following the path of dengue and chikungunya? Lancet 386, 243–244.
Musso, D. and Gubler, D.J. 2016. Zika virus. Clin. Microbiol. Rev. 29, 487–524.
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.
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.
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.
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.
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.
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.
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.
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.
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. http://www.paho.org/hq/index.php?option=com_docman&task=doc_view &Itemid=270&gid=36937&lang=en.
PAHO/WHO. 2017. Zika -epidemiological update. Pan American Health Organization/World Health Organization, Washington, D.C. January 12, 2017. http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid= 37671&lang=en.
Paranjape, S.M. and Harris, E. 2010. Control of dengue virus translation and replication. Curr. Top. Microbiol. Immunol. 338, 15–34.
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.
Perera-Lecoin, M., Meertens, L., Carnec, X., and Amara, A. 2013. Flavivirus entry receptors: an update. Viruses 6, 69–88.
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.
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.
Pierson, T.C. and Diamond, M.S. 2012. Degrees of maturity: the complex structure and biology of flaviviruses. Curr. Opin. Virol. 2, 168–175.
Pierson, T.C. and Kielian, M. 2013. Flaviviruses: braking the entering. Curr. Opin. Virol. 3, 3–12.
Pijlman, G.P. 2014. Flavivirus RNAi suppression: decoding noncoding RNA. Curr. Opin. Virol. 7, 55–60.
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.
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.
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.
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.
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.
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.
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.
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.
Robin, Y. and Mouchet, J. 1975. Serological and entomological study on yellow fever in Sierra Leone. Bull. Soc. Pathol. Exot. Filiales 68, 249–258.
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.
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.
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.
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.
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.
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.
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.
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.
Selisko, B., Wang, C., Harris, E., and Canard, B. 2014. Regulation of Flavivirus RNA synthesis and replication. Curr. Opin. Virol. 9, 74–83.
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.
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.
Simpson, D.I. 1964. Zika virus infection in man. Trans. R. Soc. Trop. Med. Hyg. 58, 335–338.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Stiasny, K., Fritz, R., Pangerl, K., and Heinz, F.X. 2011. Molecular mechanisms of flavivirus membrane fusion. Amino Acids 41, 1159–1163.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
WHO. 2015. Zika virus outbreaks in the Americas. Wkly. Epidemiol. Rec. 90, 609–610.
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. http://www.who.int/ mediacentre/news/statements/2016/1st-emergency-committeezika/ en/.
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. http://www.who.int/mediacentre/news/statements/ 2016/zika-fifth-ec/en/.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Zuker, M. 2003. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406–3415.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yun, SI., Lee, YM. Zika virus: An emerging flavivirus. J Microbiol. 55, 204–219 (2017). https://doi.org/10.1007/s12275-017-7063-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12275-017-7063-6