Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic

Zhu, Zheng; Chan, Jasper Fuk-Woo; Tee, Kah-Meng; Choi, Garnet Kwan-Yue; Lau, Susanna Kar-Pui; Woo, Patrick Chiu-Yat; Tse, Herman; Yuen, Kwok-Yung

Zika virus (ZIKV) is an emerging mosquito-borne human-pathogenic flavivirus that has been mostly neglected due to its mild clinical manifestations and limited spread in restricted geographical regions in the first 60 years after its discovery. 1 ZIKV was first isolated from the serum of a febrile sentinel rhesus macaque in 1947 in Zika Forest of Uganda. 2 Between 1947 and 2006, o20 cases of human ZIKV infection were reported in the literature. 1 These cases were geographically restricted in certain African (African lineage) and Southeast Asian (Asian lineage) countries. The first documented sizable outbreak of human ZIKV infection outside Africa and Asia occurred on Yap Island of the French States of Micronesia in 2007, during which 73% of the Yap population became infected. 3 ZIKV then spread to other Pacific islands, and arrived in the western hemisphere in 2014 (Easter Island, Chile). [4] [5] [6] Since then, many countries in the Americas have reported autochthonous cases of ZIKV infection. Brazil alone has reported an estimated 500 000-1 500 000 human cases of ZIKV infection in 2015. 7 Although most patients with ZIKV infection are asymptomatic or have mild symptoms, life-threatening complications such as Guillain-Barré syndrome, thrombocytopenic purpura, and fatal disseminated disease in immunosuppressed hosts have been reported. 1, 3, 8 Furthermore, preliminary epidemiological and virological data suggest that congenital ZIKV infection may be associated with microcephaly and other congenital anomalies in infected fetuses. [9] [10] [11] The rapidly expanding epidemic and this suspected congenital ZIKV syndrome have led the World Health Organization to declare the ZIKV outbreak as a global public health emergency on 1 February 2016. 12 The cause of the sudden emergence and rapid spread of ZIKV since 2007 is incompletely understood. A number of possible environmental factors have been proposed. First, globalization and urbanization have allowed ZIKV and its mosquito vectors to spread beyond their original geographical habitats. Second, major sport events including the World Cup and the Va'a World Sprint Championship canoe race in Brazil in 2014 might have provided an opportunity for infected travelers to introduce the virus to Latin America. 13 Third, climate changes associated with El Niño in South America in 2015 on the background trend of global warming possibly facilitated the rapid spread of Aedes mosquitoes and ZIKV. 14 Fourth, the increased awareness of and diagnostic capability for ZIKV infection likely led to the increased detection of this previously neglected disease. In contrast, little is known about the virological factors possibly associated with the apparent change in the spread of ZIKV after 2007. Although it has been shown that the epidemic strains are phylogenetically more closely related to the Asian than the African lineage of ZIKV, a comprehensive comparative analysis between the preepidemic and epidemic strains is lacking. 15 In this study, we performed comparative genomic analysis of all the pre-epidemic and epidemic strains with complete genome or complete polyprotein sequences available in GenBank to identify possible viral factors associated with this rapidly emerging viral epidemic.