For best viewing of the website please use Mozilla Firefox or Google Chrome.
Volume 31 Issue 2
April 2016
Article Contents
Citation: Shu Shen, Junming Shi, Jun Wang, Shuang Tang, Hualin Wang, Zhihong Hu, Fei Deng. Phylogenetic analysis revealed the central roles of two African countries in the evolution and worldwide spread of Zika virus [J].VIROLOGICA SINICA, 2016, 31(2) : 118-130.  http://dx.doi.org/10.1007/s12250-016-3774-9

Phylogenetic analysis revealed the central roles of two African countries in the evolution and worldwide spread of Zika virus

  • ORCID: 0000-0002-5385-083X; 
  • Received Date: 18 March 2016
    Accepted Date: 21 April 2016
    Published Date: 26 April 2016
  • Recent outbreaks of Zika virus (ZIKV) infections in Oceania's islands and the Americas were characterized by high numbers of cases and the spread of the virus to new areas. To better understand the origin of ZIKV, its epidemic history was reviewed. Although the available records and information are limited, two major genetic lineages of ZIKV were identified in previous studies. However, in this study, three lineages were identified based on a phylogenetic analysis of all virus sequences from GenBank, including those of the envelope protein (E) and non-structural protein 5 (NS5) coding regions. The spatial and temporal distributions of the three identified ZIKV lineages and the recombination events and mechanisms underlying their divergence and evolution were further elaborated. The potential migration pathway of ZIKV was also characterized. Our findings revealed the central roles of two African countries, Senegal and Cote d'Ivoire, in ZIKV evolution and genotypic divergence. Furthermore, our results suggested that the outbreaks in Asia and the Pacific islands originated from Africa. The results provide insights into the geographic origins of ZIKV outbreaks and the spread of the virus, and also contribute to a better understanding of ZIKV evolution, which is important for the prevention and control of ZIKV infections.
  • 加载中
  • 10.1007s12250-016-3774-9.pdf
    1. Alera MT, Hermann L, Tac-An IA, Klungthong C, Rutvisuttinunt W, Manasatienkij W, Villa D, Thaisomboonsuk B, Velasco JM, Chinnawirotpisan P, Lago CB, Roque VG, Jr., Macareo LR, Srikiatkhachorn A, Fernandez S, Yoon IK. 2015. Zika virus infection, Philippines, 2012. Emerg Infect Dis, 21: 722-724.
        doi: 10.3201/eid2104.141707

    2. Asahina S. 1970. Transoceanic flight of mosquitoes on the Northwest Pacific. Jpn J Med Sci Biol, 23: 255-258.
        doi: 10.7883/yoken1952.23.255

    3. Baronti C, Piorkowski G, Charrel RN, Boubis L, Leparc-Goffart I, de Lamballerie X. 2014. Complete coding sequence of zika virus from a French polynesia outbreak in 2013. Genome Announc, 2.

    4. Berthet N, Nakoune E, Kamgang B, Selekon B, Descorps-Declere S, Gessain A, Manuguerra JC, 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.
        doi: 10.1089/vbz.2014.1607

    5. Buathong R, Hermann L, Thaisomboonsuk B, Rutvisuttinunt W, Klungthong C, Chinnawirotpisan P, Manasatienkij W, Nisalak A, Fernandez S, Yoon IK, Akrasewi P, Plipat T. 2015. Detection of Zika Virus Infection in Thailand, 2012-2014. Am J Trop Med Hyg, 93: 380-383.
        doi: 10.4269/ajtmh.15-0022

    6. Cao-Lormeau VM, Roche C, Teissier A, Robin E, Berry AL, Mallet HP, Sall AA, Musso D. 2014. Zika virus, French polynesia, South pacific, 2013. Emerg Infect Dis, 20: 1085-1086.

    7. Darwish MA, Hoogstraal H, Roberts TJ, Ahmed IP, Omar F. 1983. A Sero-Epidemiological Survey for Certain Arboviruses (Togaviridae) in Pakistan. Trans R Soc Trop Med Hyg, 77: 442-445.
        doi: 10.1016/0035-9203(83)90106-2

    8. Dick GW, Kitchen SF, Haddow AJ. 1952. Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg, 46: 509-520.
        doi: 10.1016/0035-9203(52)90042-4

    9. Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB. 2009. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med, 360: 2536-2543.
        doi: 10.1056/NEJMoa0805715

    10. Dupont-Rouzeyrol M, O'Connor O, Calvez E, Daures M, John M, Grangeon JP, Gourinat AC. 2015. Co-infection with Zika and dengue viruses in 2 patients, New Caledonia, 2014. Emerg Infect Dis, 21: 381-382.
        doi: 10.3201/eid2102.141553

    11. Enfissi A, Codrington J, Roosblad J, Kazanji M, Rousset D. 2016a. Zika virus genome from the Americas. Lancet, 387: 227-228.
        doi: 10.1016/S0140-6736(16)00003-9

    12. Enfissi A, Codrington J, Roosblad J, Kazanji M, Rousset D. 2016b. Zika virus genome from the Americas. Lancet, 387: 227-228.
        doi: 10.1016/S0140-6736(16)00003-9

    13. Enserink M. 2015. INFECTIOUS DISEASES. An obscure mosquito-borne disease goes global. Science, 350: 1012-1013.

    14. Faye O, Freire CC, Iamarino A, Faye O, de Oliveira JV, Diallo M, Zanotto PM, Sall AA. 2014. Molecular evolution of Zika virus during its emergence in the 20(th) century. PLoS Negl Trop Dis, 8: e2636.
        doi: 10.1371/journal.pntd.0002636

    15. Filipe AR, Martins CM, Rocha H. 1973. Laboratory infection with Zika virus after vaccination against yellow fever. Arch Gesamte Virusforsch, 43: 315-319.
        doi: 10.1007/BF01556147

    16. Fonseca K, Meatherall B, Zarra D, Drebot M, MacDonald J, Pabbaraju K, Wong S, Webster P, Lindsay R, Tellier R. 2014. First case of Zika virus infection in a returning Canadian traveler. Am J Trop Med Hyg, 91: 1035-1038.
        doi: 10.4269/ajtmh.14-0151

    17. Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow AD, Lanciotti RS, Tesh RB. 2011. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis, 17: 880-882.
        doi: 10.3201/eid1705.101939

    18. Grard G, Caron M, Mombo IM, Nkoghe D, Mboui Ondo S, Jiolle D, Fontenille D, Paupy C, Leroy EM. 2014. Zika virus in Gabon (Central Africa)--2007: a new threat from Aedes albopictus? PLoS Negl Trop Dis, 8: e2681.
        doi: 10.1371/journal.pntd.0002681

    19. Haddow AD, Schuh AJ, Yasuda CY, Kasper MR, Heang V, Huy R, Guzman H, Tesh RB, Weaver SC. 2012. Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage. PLoS Negl Trop Dis, 6: e1477.
        doi: 10.1371/journal.pntd.0001477

    20. Hancock WT, Marfel M, Bel M. 2014. Zika virus, French Polynesia, South Pacific, 2013. Emerg Infect Dis, 20: 1960.
        doi: 10.3201/eid2011.141380

    21. Hayes EB. 2009. Zika virus outside Africa. Emerg Infect Dis, 15: 1347-1350.
        doi: 10.3201/eid1509.090442

    22. Heang V, Yasuda CY, Sovann L, Haddow AD, Travassos da Rosa AP, Tesh RB, Kasper MR. 2012. Zika virus infection, Cambodia, 2010. Emerg Infect Dis, 18: 349-351.
        doi: 10.3201/eid1802.111224

    23. Jan C, Languillat G, Renaudet J, Robin Y. 1978. A serological survey of arboviruses in Gabon. Bull Soc Pathol Exot Filiales, 71: 140-146. (In French)

    24. Kindhauser MK, Allen T, Frank V, Santhana RS, Dye C. 2016. Zika: the origin and spread of a mosquito-borne virus. Bull World Health Organ.

    25. Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR. 2008. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis, 14: 1232-1239.
        doi: 10.3201/eid1408.080287

    26. Leung GH, Baird RW, Druce J, Anstey NM. 2015. Zika Virus Infection in Australia Following a Monkey Bite in Indonesia. Southeast Asian J Trop Med Public Health, 46: 460-464.

    27. Macnamara FN. 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.
        doi: 10.1016/0035-9203(54)90006-1

    28. Marchette NJ, Garcia R, Rudnick A. 1969. Isolation of Zika virus from Aedes aegypti mosquitoes in Malaysia. Am J Trop Med Hyg, 18: 411-415.
        doi: 10.4269/ajtmh.1969.18.411

    29. Martin DP, Lemey P, Lott M, Moulton V, Posada D, Lefeuvre P. 2010. RDP3: a flexible and fast computer program for analyzing recombination. Bioinformatics, 26: 2462-2463.
        doi: 10.1093/bioinformatics/btq467

    30. Mlakar J, Korva M, Tul N, Popovic M, Poljsak-Prijatelj M, Mraz J, Kolenc M, Resman Rus K, Vesnaver Vipotnik T, Fabjan Vodusek V, Vizjak A, Pizem J, Petrovec M, Avsic Zupanc T. 2016. Zika Virus Associated with Microcephaly. N Engl J Med. 374: 951-958.
        doi: 10.1056/NEJMoa1600651

    31. Moore DL, Causey OR, Carey DE, Reddy S, Cooke AR, Akinkugbe FM, David-West TS, Kemp GE. 1975. Arthropod-borne viral infections of man in Nigeria, 1964-1970. Ann Trop Med Parasitol, 69: 49-64.
        doi: 10.1080/00034983.1975.11686983

    32. Musso D, Cao-Lormeau VM, Gubler DJ. 2015.Zika virus: following the path of dengue and chikungunya? Lancet, 386: 243-244.
        doi: 10.1016/S0140-6736(15)61273-9

    33. Oehler E, Watrin L, Larre P, Leparc-Goffart I, Lastere S, Valour F, Baudouin L, Mallet H, Musso D, Ghawche F. 2014. Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013. Euro Surveill, 19.

    34. Olson JG, Ksiazek TG, Gubler DJ, Lubis SI, Simanjuntak G, Lee VH, Nalim S, Juslis K, 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.
        doi: 10.1080/00034983.1983.11811687

    35. Olson JG, Ksiazek TG, Suhandiman, Triwibowo. 1981. Zika virus, a cause of fever in Central Java, Indonesia. Trans R Soc Trop Med Hyg, 75: 389-393.
        doi: 10.1016/0035-9203(81)90100-0

    36. Pond WL. 1963. Arthropod-Borne Virus Antibodies in Sera from Residents of South-East Asia. Trans R Soc Trop Med Hyg, 57: 364-371.
        doi: 10.1016/0035-9203(63)90100-7

    37. Roth A, Mercier A, Lepers C, Hoy D, Duituturaga S, Benyon E, Guillaumot L, 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.

    38. Saluzzo JF, Gonzalez JP, Herve JP, Georges AJ. 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.

    39. Simpson DI. 1964. Zika Virus Infection in Man. Trans R Soc Trop Med Hyg, 58: 335-338.
        doi: 10.1016/0035-9203(64)90200-7

    40. Smithburn KC. 1952. Neutralizing antibodies against certain recently isolated viruses in the sera of human beings residing in East Africa. J Immunol, 69: 223-234.

    41. Smithburn KC, Taylor RM, Rizk F, Kader A. 1954. Immunity to Certain Arthropod-Borne Viruses among Indigenous Residents of Egypt. Am J Trop Med Hyg, 3: 9-18.
        doi: 10.4269/ajtmh.1954.3.9

    42. Tappe D, Nachtigall S, Kapaun A, Schnitzler P, Gunther S, Schmidt-Chanasit J. 2015. Acute Zika Virus Infection after Travel to Malaysian Borneo, September 2014. Emerg Infect Dis, 21: 911-913.
        doi: 10.3201/eid2105.141960

    43. Tognarelli J, Ulloa S, Villagra E, Lagos J, Aguayo C, Fasce R, Parra B, Mora J, Becerra N, Lagos N, Vera L, Olivares B, Vilches M, Fernandez J. 2015. A report on the outbreak of Zika virus on Easter Island, South Pacific, 2014. Arch Virol. 161: 665-668.

    44. Urdaneta-Marquez L, Failloux AB. 2011. Population genetic structure of Aedes aegypti, the principal vector of dengue viruses. Infect Genet Evol, 11: 253-261.
        doi: 10.1016/j.meegid.2010.11.020

    45. Waehre T, Maagard A, Tappe D, Cadar D, Schmidt-Chanasit J. 2014. Zika virus infection after travel to Tahiti, December 2013. Emerg Infect Dis, 20: 1412-1414.
        doi: 10.3201/eid2008.140302

    46. Waggoner JJ, Pinsky BA. 2016. Zika Virus: Diagnostics for an Emerging Pandemic Threat. J Clin Microbiol, 54: 860-867.
        doi: 10.1128/JCM.00279-16

    47. Wallace RG, Hodac H, Lathrop RH, Fitch WM. 2007. A statistical phylogeography of influenza A H5N1. Proc Natl Acad Sci U S A, 104: 4473-4478.
        doi: 10.1073/pnas.0700435104

    48. Weaver SC, Lecuit M. 2015. Chikungunya virus and the global spread of a mosquito-borne disease. N Engl J Med, 372: 1231-1239.
        doi: 10.1056/NEJMra1406035

    49. World Health Organization. 2014. A global brief on vector-borne diseases.

    50. Zammarchi L, Stella G, Mantella A, Bartolozzi D, Tappe D, Gunther S, Oestereich L, Cadar D, Munoz-Fontela C, Bartoloni A, Schmidt-Chanasit J. 2015. Zika virus infections imported to Italy: clinical, immunological and virological findings, and public health implications. J Clin Virol, 63: 32-35.
        doi: 10.1016/j.jcv.2014.12.005

  • 加载中

Figures(4) / Tables(3)

Article Metrics

Article views(134) PDF downloads(0) Cited by()

Ralated
Proportional views
    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Phylogenetic analysis revealed the central roles of two African countries in the evolution and worldwide spread of Zika virus

    • State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

    Abstract: Recent outbreaks of Zika virus (ZIKV) infections in Oceania's islands and the Americas were characterized by high numbers of cases and the spread of the virus to new areas. To better understand the origin of ZIKV, its epidemic history was reviewed. Although the available records and information are limited, two major genetic lineages of ZIKV were identified in previous studies. However, in this study, three lineages were identified based on a phylogenetic analysis of all virus sequences from GenBank, including those of the envelope protein (E) and non-structural protein 5 (NS5) coding regions. The spatial and temporal distributions of the three identified ZIKV lineages and the recombination events and mechanisms underlying their divergence and evolution were further elaborated. The potential migration pathway of ZIKV was also characterized. Our findings revealed the central roles of two African countries, Senegal and Cote d'Ivoire, in ZIKV evolution and genotypic divergence. Furthermore, our results suggested that the outbreaks in Asia and the Pacific islands originated from Africa. The results provide insights into the geographic origins of ZIKV outbreaks and the spread of the virus, and also contribute to a better understanding of ZIKV evolution, which is important for the prevention and control of ZIKV infections.

    • Zika virus (ZIKV) is an emerging pathogen, transmitted by Aedes species, that belongs to the genus Flavivirus of the family Flaviviridae. ZIKV-infected patients usually have symptoms characterized by fever, headache, rash, myalgia, arthralgia, and conjunctivitis, which are similar to the clinical symptoms caused by Dengue virus (DENV) or Chikungunya virus (CHIKV) infection. Thus, ZIKV could be easily misdiagnosed as Dengue (DEN) or Chikungunya (CHIK) fever (Haddow et al., 2012). A body of evidence has shown that ZIKV infection is associated with the neurological disorders microcephaly (Mlakar et al., 2016) and Guillainâ€"Barré syndrome (Oehler et al., 2014). Further, not only has the number of ZIKV cases increased in recent years, but the disease has spread to new regions that had no previous record of Zika disease. Thus, Zika disease has become a serious public health problem. The worldwide dispersal and transmission of ZIKV should be of great concern to researchers, and their study will contribute to the prevention and control of outbreaks and epidemics of Zika disease.

      ZIKV first emerged in Africa. It was first isolated in 1947 from a sentinel monkey in Uganda (Dick et al., 1952). The first ZIKV infection in human was identified in Uganda and Tanzania in 1952 (Smithburn, 1952). ZIKV was detected in humans, Aedes species and animals in African countries in the following decades (Macnamara, 1954; Simpson, 1964; Faye et al., 2014). Then, ZIKV spread to Southern Asia. It was isolated from Aedes aegypti in Malaysia in 1966 (Marchette et al., 1969). The wide distribution of ZIKV in Indonesia, Malaysia, and Pakistan was further revealed by serological investigations (Kindhauser et al., 2016). Subsequently, ZIKV spread to countries in Oceania and the Americas. The first large outbreak of Zika disease in humans occurred on the Pacific island of Yap in the Federated States of Micronesia in 2007 (Lanciotti et al., 2008; Duffy et al., 2009). ZIKV was then identified from Suriname (Enfissi et al., 2016b) in South America, and on other Pacific Islands including French Polynesia (Berthet et al., 2014; Cao-Lormeau et al., 2014; Hancock et al., 2014), Easter Island of Chile (Tognarelli et al., 2015), the Cook Islands (Roth et al., 2014), and New Caledonia (Roth et al., 2014; Dupont-Rouzeyrol et al., 2015). Imported cases were also identified in countries of the Americas and Europe (Foy et al., 2011; Waehre et al., 2014; Zammarchi et al., 2015; Kindhauser et al., 2016). Until March 2016, a total of 10 imported infectious cases had been diagnosed in China. A brief review of ZIKV's history found that ZIKV migration seems to have followed the same path as CHIKV and DENV, which were first described in Africa and then spread to Asia before becoming distributed worldwide (Musso et al., 2015). Although the future is unpredictable, ZIKV has the potential to spread globally through the increasing international movement of humans, goods, and animals for travel and business, and could represent a major threat to human health. Investigating the migration pathways of ZIKV can help to shed light on the origins of ZIKV epidemics.

      Two major genetic lineages of ZIKV strains associated with its geographic distribution, namely the African and Asian lineages, have been characterized and limited ZIKV nucleic acid sequences are available (Haddow et al., 2012; Faye et al., 2014). The strains identified from recent epidemics in the Americas belonged to the Asian lineage (Enfissi et al., 2016b), suggesting that strains from Asia and the Americas are closely related. However, as only limited nucleic acid sequences of ZIKV strains are available in GenBank for phylogenetic analysis and other bio-informatics analyses (Haddow et al., 2012; Faye et al., 2014), knowledge of the genetic relationships of ZIKV strains and the geographic origins of ZIKV epidemics is limited. This study focuses on the phylogenetic relationships among ZIKV strains, the spatial and temporal distributions of ZIKV lineages, and the potential recombination and migration of ZIKV among different countries and territories. The results reveal the geographic origins and migration patterns of ZIKV epidemics, which will be further discussed.

    • ZIKV sequences deposited in GenBank until February 4, 2016 were used for phylogenetic analysis. Sequences were aligned by CLUSTAL W (MEGA 5.0). Phylogenetic trees were constructed for the full-length genome, the envelope protein (E) coding region, and the non-structural protein 5 (NS5) coding region by MEGA 5.0 using both the neighbor-joining (NJ) and maximum-likelihood (ML) methods, and tested by the bootstrap method with 1000 replicates. The sequence of Spondweni virus (GenBank accession number: DQ859064) was included as the outgroup control.

    • Recombination events were detected by the RDP software package using seven recombination detection methods (Martin et al., 2010) based on the concatenate sequences of E protein coding region and NS5 protein coding region. Recombination events that were significant by at least two methods (P < 0.05) and had an RDP recombination consensus score (RDPRCS) of more than 0.60 were considered to be confirmed events. Recombination events that were significant by at least two methods (P < 0.05) and had an RDPRCS score between 0.4â€"0.6 were considered to be possible events. Events that did not meet these criteria were rejected.

    • The ZIKV spread pathway was analyzed using the MIGRAPHYLA package (Wallace et al., 2007) based on the NS5 tree. The reliability of each migration event was evaluated using a Monte Carlo simulation process by rand omizing the location of the leaf nodes while retaining the tree topologies.

    • Since the first identification and isolation of ZIKV in 1947 (Dick et al., 1952), records of ZIKV were sparse until the last decade (Kindhauser et al., 2016). Despite the limited numbers of ZIKV sequences available in GenBank, two major lineages of ZIKV, the African and Asian lineages, were characterized in several previous studies (Haddow et al., 2012; Faye et al., 2014). This current study also characterized these two major lineages by constructing a phylogenetic tree for the full-length genome sequences of 23 ZIKV strains (Figure 1). However, in contrast to previous reports on ZIKV genetic relationships based on the limited number of sequences available (Haddow et al., 2012; Faye et al., 2014; Enfissi et al., 2016b), we found that, for the first time, three lineages of ZIKV could be clustered based on the robust E and NS5 trees. These three lineages were designated as the Asian/American lineage, African lineage 1, and African lineage 2, respectively, according to their geographic distributions. Because only partial sequences of the several strains clustered in the additional African lineage 2 were available, this cluster could not be identified by the previous phylogenetic analyses conducted using fewer ZIKV strains.

      From our phylogenetic analyses, it is noted that African lineage 2, which has mainly been isolated from Senegal, diverged earlier than the other two lineages, suggesting that the ancestral strains of ZIKV may derive from Senegal. Then, we found that at least two genotypes of ZIKV have co-circulated in Senegal. So, it seems highly probable that recombination between different genotypes has happened in Senegal to generate recombinants with new genotypes. Subsequently, our analysis of recombination events revealed that ZIKV strains from Senegal were more frequently involved in recombination events than other strains. Therefore, strains from Senegal played important roles in ZIKV evolution and divergence. Although it was not so much involved as Senegal, Cote d'Ivoire is also an important country related to ZIKV evolution. Co-circulation of ZIKV strains of different genotypes occurred in Cote d'Ivoire, as African lineage 2, which showed an early divergence from other lineages, included one strain from Cote d'Ivoire (ArA1465) in the E tree (Figure 2A) and other strains from Cote d'Ivoire were clustered in African lineage 1 (Figure 2A and 2B). Moreover, strains from Cote d'Ivoire were also involved in the recombination events. Taken together, our phylogenetic analysis revealed important phylogeographic roles of Senegal and Cote d'Ivoire in ZIKV evolution and divergence.

      The migration of ZIKV was elaborated to illustrate the potential pathways for the spread of ZIKV and the geographic origins of recent ZIKV epidemics. Senegal and Cote d'Ivoire were identified to be the countries that had most frequently exported and imported ZIKV strains. Furthermore, ZIKV migrated from Senegal to the Asian countries and Pacific island s where confirmed autochthonous cases were identified, suggesting Senegal as the geographic origin of all known ZIKV epidemics outside Africa. These results are supported by a previous report that illustrated the frequent movement of ZIKV between Senegal and Cote d'Ivoire between 1920 and 1985, and mentioned that the ZIKV lineage from Africa spread to Malaysia around 1945, and to Micronesia around 1960 (Faye et al., 2014). ZIKV export from Senegal directly to Canada was also detected by our analysis using MIGRAPHYLA. However, no autochthonous cases were confirmed in Canada and the patient had recently returned from Thailand (Fonseca et al., 2014). It is possible that the pathway from Senegal to Canada was identified by MIGRAPHYLA because the sequence of the strain PLCalZV that was imported to Canada is mostly similar to that of the strain SV0127/14 from Thailand, which had already imported ZIKV strains from Senegal (Figure 2B). The analyses of ZIKV recombination and migration were conducted according to the phylogenetic analysis in the current study, which are estimated based on the available sequences so far. So the amount of available ZIKV sequences may influence the results of the analyses.

      The human cases showed clinical manifestations of ZIKV infections that could be easily mistaken for DEN or CHIK fever. The latter two diseases emerged earlier and were much more commonly diagnosed than ZIKV infections in Africa (Faye et al., 2014). Based on their characterization of the history of ZIKV outbreaks and epidemics globally, Dr. Musso, and his colleagues reported that the spread of ZIKV seems to have followed the same path as DENV and CHIKV and that the potential for ZIKV epidemics might be overwhelming (Musso et al., 2015). The areas at risk of DENV and CHIKV transmission or with identified cases mostly matched with the areas of autochthonous ZIKV outbreaks (Figure 3A). Furthermore, the areas at risk of DENV and CHIKV are all located within the habitat areas of the Ae. Aegypti mosquito (Urdaneta-Marquez and Failloux, 2011), which is one of the principal arthropod vectors of ZIKV (Hayes, 2009), DENV, and CHIKV (World Health Organization, 2014; Weaver and Lecuit, 2015). Although wind-blown mosquitoes can migrate over the sea to distances of several hundred kilometers (Asahina, 1970), it is more likely that the migration of ZIKV over the great distances between continents was achieved as a result of increasing international travel and trade activities by which infected persons and animal hosts were transported to countries that were previously free from ZIKV (Duffy et al., 2009). Further, as the world's human population mostly gathers and lives in areas inhabited by Ae. Aegypti and other mosquitoes, the potential for the worldwide spread of ZIKV is likely to be still increasing. Therefore, it is important to investigate the relationship between ZIKV migration and the distributions and life cycles of mosquito vectors as well as international transport and trade activities. The information that can be provided by such studies will greatly help to prevent and control ZIKV outbreaks worldwide.

    • This work was supported by the Science and Technology Basic Work Program (2013FY113500) from the Ministry of Science and Technology of China.

    • This article does not contain any studies with human or animal subjects performed by any of the authors. The authors declare no conflicts of interest.

    • SS and FD conceived of the study. JMS performed the ZIKV recombination detection and migration analyses. JW downloaded ZIKV sequences available in GenBank and generated the sequence datasets for phylogenetic analysis. ST collected all the information of ZIKV outbreaks and epidemics as listed in Table 1. SS constructed the phylogenetic trees, analyzed all the results, and wrote the first version of the manuscript. HLW, ZHH and FD checked and finalized the manuscript.

    • Strains Locations Time Lineages
      Full-length E gene NS5 gene
      ArD157995 Senegal 2001 A1 A1 A1
      ArA1465 Cote d'Ivoire 1980 N/A A2 A1
      Notes: A1, African lineage 1; A2, African lineage 2; N/A, not applicable.

      Table Table S1.  Strains of discrepancies among tree topology by visual comparison

    Figure (4)  Table (3) Reference (50)

    目录

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return