title: Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic.
abstract: Less than 20 sporadic cases of human Zika virus (ZIKV) infection were reported in Africa and Asia before 2007, but large outbreaks involving up to 73% of the populations on the Pacific islands have started since 2007, and spread to the Americas in 2014. Moreover, the clinical manifestation of ZIKV infection has apparently changed, as evident by increasing reports of neurological complications, such as Guillain-Barré syndrome in adults and congenital anomalies in neonates. We comprehensively compared the genome sequences of pre-epidemic and epidemic ZIKV strains with complete genome or complete polyprotein sequences available in GenBank. Besides the reported phylogenetic clustering of the epidemic strains with the Asian lineage, we found that the topology of phylogenetic tree of all coding regions is the same except that of the non-structural 2B (NS2B) coding region. This finding was confirmed by bootscan analysis and multiple sequence alignment, which suggested the presence of a fragment of genetic recombination at NS2B with that of Spondweni virus. Moreover, the representative epidemic strain possesses one large bulge of nine bases instead of an external loop on the first stem-loop structure at the 3'-untranslated region just distal to the stop codon of the NS5 in the 1947 pre-epidemic prototype strain. Fifteen amino acid substitutions are found in the epidemic strains when compared with the pre-epidemic strains. As mutations in other flaviviruses can be associated with changes in virulence, replication efficiency, antigenic epitopes and host tropism, further studies would be important to ascertain the biological significance of these genomic changes.
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
authors.forename: Jasper Fuk-Woo
authors.initials: JF
authors.lastname: Chan
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Kah-Meng
authors.initials: KM
authors.lastname: Tee
authors.affiliation: Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Garnet Kwan-Yue
authors.initials: GK
authors.lastname: Choi
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
authors.forename: Susanna Kar-Pui
authors.initials: SK
authors.lastname: Lau
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
authors.forename: Patrick Chiu-Yat
authors.initials: PC
authors.lastname: Woo
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
authors.forename: Herman
authors.initials: H
authors.lastname: Tse
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.|Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.|Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000328:Adult; D000349:Africa / Q000453:epidemiology; D000569:Americas / Q000453:epidemiology; D019943:Amino Acid Substitution; D001208:Asia / Q000453:epidemiology; D001483:Base Sequence; D002874:Chromosome Mapping; D016000:Cluster Analysis; D058872:Epidemics; D005814:Genes, Viral; D016679:Genome, Viral; D006801:Humans; D009154:Mutation; D010139:Pacific Islands / Q000453:epidemiology; D010802:Phylogeny; D011995:Recombination, Genetic; D016415:Sequence Alignment; D000071244:Zika Virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D000071243:Zika Virus Infection / Q000453:epidemiology / Q000821:virology*