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Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage - PubMed

Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage

Andrew D Haddow et al. PLoS Negl Trop Dis. 2012.

Abstract

Background: Zika virus (ZIKV) is a mosquito-borne flavivirus distributed throughout much of Africa and Asia. Infection with the virus may cause acute febrile illness that clinically resembles dengue fever. A recent study indicated the existence of three geographically distinct viral lineages; however this analysis utilized only a single viral gene. Although ZIKV has been known to circulate in both Africa and Asia since at least the 1950s, little is known about the genetic relationships between geographically distinct virus strains. Moreover, the geographic origin of the strains responsible for the epidemic that occurred on Yap Island, Federated States of Micronesia in 2007, and a 2010 pediatric case in Cambodia, has not been determined.

Methodology/principal findings: To elucidate the genetic relationships of geographically distinct ZIKV strains and the origin of the strains responsible for the 2007 outbreak on Yap Island and a 2010 Cambodian pediatric case of ZIKV infection, the nucleotide sequences of the open reading frame of five isolates from Cambodia, Malaysia, Nigeria, Uganda, and Senegal collected between 1947 and 2010 were determined. Phylogenetic analyses of these and previously published ZIKV sequences revealed the existence of two main virus lineages (African and Asian) and that the strain responsible for the Yap epidemic and the Cambodian case most likely originated in Southeast Asia. Examination of the nucleotide and amino acid sequence alignments revealed the loss of a potential glycosylation site in some of the virus strains, which may correlate with the passage history of the virus.

Conclusions/significance: The basal position of the ZIKV strain isolated in Malaysia in 1966 suggests that the recent outbreak in Micronesia was initiated by a strain from Southeast Asia. Because ZIKV infection in humans produces an illness clinically similar to dengue fever and many other tropical infectious diseases, it is likely greatly misdiagnosed and underreported.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Zika virus nucleotide and amino acid alignments.

Neighbor-joining phylogeny generated from open reading frame nucleotide sequences of Zika virus strains. The tree was rooted with Spondweni virus (GenBank accession number DQ859064). The scale at the bottom of the tree represents genetic distance in nucleotide substitutions per site. Numbers at the nodes represent percent bootstrap support values based on 1,000 replicates. Isolates are represented according to strain name, country of origin, and year of isolation. The lineage of each virus is indicated to the right of the tree. *Strains sequenced in this study.

Figure 2
Figure 2. Zika virus phylogeny.

Nucleotide (top) and amino acid (bottom) sequences of the envelope protein/gene of Zika virus strains showing the deletions in the potential glycosylation sites of the MR 766 (Uganda, 1947) and the IbH 30656 (Nigeria, 1968) strains. Deletions are indicated by dashes. The “N” at position 467 of the P6-740 strain (Malaysia, 1966) represents an equally weighted double population of the nucleotides “C” and “T”. This translates to an “X” at position 165 of the amino acid alignment.

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