Risk Assessment and Genomic Characterization of Zika Virus in China and Its Surrounding Areas
Zika virus (ZIKV) has emerged as a significant global pathogen, raising substantial public health concerns. While ZIKV was first isolated in Uganda in 1947, it was not until the 2015 outbreak in Brazil that it gained widespread attention. Since then, ZIKV has spread across the Americas and other regions, including Asia. China, with its frequent international travel and suitable climate for mosquito vectors, has reported several imported cases of ZIKV. This study aims to comprehensively characterize the ZIKV strains isolated from cases reported in China and assess the risk of ZIKV transmission in the region.
ZIKV is a single-stranded, positive-sense RNA virus belonging to the Flaviviridae family. It is primarily transmitted through the bites of Aedes aegypti and Aedes albopictus mosquitoes but can also spread through maternal-fetal transmission, blood transfusions, and sexual activities. While ZIKV infections typically cause mild, self-limiting febrile illness, they can also lead to severe neurological complications such as Guillain-Barré syndrome and adverse fetal outcomes like microcephaly.
The study utilized a comprehensive approach to analyze ZIKV genomic sequences retrieved from the National Center for Biotechnology Information (NCBI) database. The sequences were selected based on stratified sampling, ensuring a representative sample of ZIKV strains from China and surrounding areas. The analysis included recombination event detection, maximum likelihood (ML) phylogenetic analysis, molecular clock analysis, selection pressure analysis, and amino acid substitution analysis to reconstruct the epidemiology and molecular transmission of ZIKV.
A total of 88 ZIKV sequences were analyzed, including 18 from China and 70 from 16 selected countries. The analysis revealed that recombination events are rare in the ZIKV Asian lineage. The ZIKV genomes generally underwent episodic positive selection at 17 sites, with only one site under pervasive positive selection. All ZIKV strains imported into China belonged to the Asian lineage and were assigned into two clusters: a Venezuela-origin cluster (Cluster A) and a Samoa-origin cluster (Cluster B), both with a common ancestor from French Polynesia.
The time of the most recent common ancestors (TMRCA) of Cluster A was dated to approximately November 2013, while Cluster B was dated to August 2014. Cluster B exhibited more variability than Cluster A, but no biologically significant varied sites were identified. The study also found that ZIKV strains in Southeast Asia are independent from those involved in the American epidemics.
The evolutionary rate of ZIKV genomes was estimated to be 8.61 × 10^-4 substitutions per site per year. The ML phylogenetic analysis of the complete coding regions of the 88 sequences indicated distinct Asian and African lineages. The African lineage consists of three independent clusters: Senegal, Uganda, and Nigeria. The Asian lineage includes all the recorded outbreaks or endemic circulations of ZIKV in recent decades. All strains imported into China belong to the Asian lineage.
The TempEst plot showed a positive correlation between genetic divergence and sampling time in all sequences, with a stronger correlation within the Asian lineage. The Bayesian molecular clock phylogenies estimated the evolutionary rate and provided insights into the temporal spread of ZIKV. The TMRCA of the Venezuela-origin cluster in China was dated to approximately November 2013, while the Samoa-origin cluster was dated to August 2014. This indicates two independent introductions of ZIKV into China.
The selection pressure analyses revealed evidence of episodic diversifying selection in three out of 165 branches in the phylogeny of the 88 sequences. However, no episodic diversifying selection was identified on internal nodes. The mixed effects model of evolution (MEME) detected episodic positive/diversifying selection at 17 sites, but no sites were detected by the single likelihood ancestor counting (SLAC) method. One positively selected site (amino acid site 2449) was detected by the Fast, Unconstrained Bayesian AppRoximation (FUBAR) method.
The amino acid substitution analysis compared the genetic variation in ZIKV clusters A and B in China, as well as clusters in Singapore, French Polynesia, and Malaysia. The analysis identified eight amino acid sites that varied between Cluster A and Cluster B in China, with four of these sites located in the NS5 protein. The structural models of the NS5 protein predicted by Swiss-Model showed similar structures, indicating that the amino acid substitutions did not significantly alter the protein’s structure.
The study concluded that the genetic evolution of ZIKV is generally conservative. There were two independent introductions of ZIKV into China, and the country is at risk of autochthonous transmission due to high-risk surrounding areas. Southeast Asia, in particular, has a high risk of originating the next large-scale epidemic ZIKV strains.
The findings of this study provide valuable insights into the genetic evolution and transmission dynamics of ZIKV in China and its surrounding areas. The comprehensive phylogenetic and genetic analyses highlight the importance of continued surveillance and research to mitigate the risks associated with ZIKV transmission. The study underscores the need for enhanced genomic data collection and analysis to better understand the epidemiology and evolution of ZIKV, particularly in regions with suitable climatic conditions for mosquito vectors.
The study also emphasizes the importance of international collaboration and data sharing to track and respond to emerging infectious diseases. By understanding the genetic relationships and transmission patterns of ZIKV, public health officials can develop more effective strategies for prevention, control, and response to potential outbreaks.
In conclusion, this study provides a detailed genomic characterization of ZIKV strains in China and surrounding areas, offering critical insights into the virus’s evolution and transmission. The findings underscore the need for ongoing vigilance and research to address the public health challenges posed by ZIKV and other emerging infectious diseases.
doi.org/10.1097/CM9.0000000000000317
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