Development of a neutralizing antibody targeting linear epitope of the envelope protein domain III of ZIKV.

Zika virus (ZIKV) infection represents an emerging infectious disease that poses an increasing threat to human health, especially after the ZIKV outbreak in Brazil in 2015. Unfortunately, there continues to be a lack of highly effective antiviral drugs or vaccines against ZIKV. In this study, we expressed the ZIKV envelope protein domain III (ZIKV EDIII) in E. coli strain BL21. The purified recombinant protein was used to immunize mice to produce monoclonal antibodies (mAbs). After 6 screening and 5 subcloning cycles, 10 monoclonal cell lines that stably produced antibodies, termed 2F5, 5B8, 6G6, 7E12, 8B6, 17E6, 19E7, 20F4, 26G6, and 37E6, were identified. The mAb 8B6 could neutralize ZIKV and recognize the ZIKV EDIII epitope (GRLITANPVITESTE). Another 9 mAbs did not exhibit neutralizing activity; however, they could specifically recognize the ZIKV EDIII and ZIKV lysate, suggesting their potential use in the diagnosis of ZIKV.

Prevalence of Zika virus in blood donations: a systematic review and meta-analysis.

BACKGROUND: Transfusion-Transmitted Zika virus (TT-ZIKV) has become an emerging threat to world blood banks due to the fast spread of ZIKV epidemics and high rate of asymptomatic infections. For the risk assessment of ZIKV infection in blood products, relevant studies in blood donations or blood donors tested for ZIKV were collected and analyzed systematically. The overall prevalence of ZIKV infection were estimated through meta-analysis and potential risk factors were detected. The results will provide important clues for the protocol design of blood screening tests. METHODS: Relevant articles about the rate of ZIKV detected in blood samples were identified from PubMed, Scopus and Web Of Science using key terms search strategy until October 7, 2017. Eligible articles were screened following inclusion and exclusion criteria. Meta-analysis and subgroup analyses were performed by software R3.4.1. Overall postdonation and posttransfusion follow-ups were analyzed. RESULTS: Ten literatures (528,947 blood samples) were included for meta-analysis. The overall pooled prevalence of ZIKV (RNA and antibody) in blood donations was 1.02% (95%CI 0.36-1.99). The pooled prevalence of ZIKV RNA in blood donations was 0.85% (95%CI 0.21-1.88) less than the pooled prevalence of anti-ZIKV antibodies 1.61% (95%CI 0.03-5.21), however the difference was not statistically significant (p = 0.52). The prevalence varied significantly in different geographical regions (p < 0.001). Blood donations were more than two times likely to be infected by ZIKV in Zika epidemic period (1.37, 95%CI 0.91-1.91) than in non-epidemic period (0.61, 95%CI 0-2.55). The prevalence of anti-ZIKV antibodies (1.61, 95%CI 0.03-5.21) was almost twice as much as ZIKV nucleic acid detected in blood donations (0.85, 95%CI 0.21-1.88). However, statistically significant differences were not observed. A total of 122 ZIKV positive blood donors were followed, of which 48 (39%) reported symptoms postdonation, but none of the 13 followed recipients reported any clinical symptoms related to Zika infection posttransfusion. CONCLUSION: The pooled prevalence of Zika infection in blood donations was 1.02%. The prevalence varied greatly and reached to high-risk level in most of the situations. The results suggest that nucleic acid tests (NAT) for blood screening and pathogen reduction/inactivation technology (PRT) should be implemented in Zika-endemic areas and appropriate strategies should be designed according to different conditions. More studies are needed in the future to provide more evidence.

Risk assessment and genomic characterization of Zika virus in China and its surrounding areas.

BACKGROUND: Zika virus (ZIKV) has emerged as a global pathogen causing significant public health concerns. China has reported several imported cases where ZIKV were carried by travelers who frequently travel between China and ZIKV-endemic regions. To fully characterize the ZIKV strains isolated from the cases reported in China and assess the risk of ZIKV transmission in China, comprehensive phylogenetic and genetic analyses were performed both on all ZIKV sequences of China and on a group of scientifically selected ZIKV sequences reported in some of the top interested destinations for Chinese travelers. METHODS: ZIKV genomic sequences were retrieved from the National Center for Biotechnology Information database through stratified sampling. Recombination event detection, maximum likelihood (ML) phylogenetic analysis, molecular clock analysis, selection pressure analysis, and amino acid substitution analysis were used to reconstruct the epidemiology and molecular transmission of ZIKV. RESULTS: The present study investigated 18 ZIKV sequences from China and 70 sequences from 16 selected countries. Recombination events rarely happens in all ZIKV Asian lineage. ZIKV genomes were generally undergone episodic positive selection (17 sites), and only one site was under pervasive positive selection. All ZIKV imported into China were Asian lineage and were assigned into two clusters: Venezuela-origin (cluster A) and Samoa-origin cluster (cluster B) with common ancestor from French Polynesia. The time of most recent common ancestors of Cluster A dated to approximately 2013/11 (95% highest posterior density [HPD] 2013/06, 2014/03) and cluster B dated to 2014/08 (95% HPD 2014/02, 2015/01). Cluster B is more variable than Cluster A in comparison with other clusters, but no varied site of biological significance was revealed. ZIKV strains in Southeast Asia countries are independent from strains in America epidemics. CONCLUSIONS: The genetic evolution of ZIKV is conservative. There are two independent introductions of ZIKV into China and China is in danger of autochthonous transmission of ZIKV because of high-risk surrounding areas. Southeast Asia areas have high risk of originating the next large-scale epidemic ZIKV strains.