ArticleViruses2018
An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo.
Article in Viruses, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Reverse Genetics of Orthoflaviviruses: Strategies for Constructing Functional or Infectious cDNA.Journal of medical virology · 2026Review
- Breaking barriers and beyond: Mechanisms and pathological implications of Zika virus traversal across blood-tissue interfaces.Virologica Sinica · 2026Review
- Development of viral infectious clones and their applications based on yeast and bacterial artificial chromosome platforms.Molecular biomedicine · 2025Review
- Immune Recognition versus Immune Evasion Systems in Zika Virus Infection.Biomedicines · 2023Review
- Influence of Zika virus 3'-end sequence and nonstructural protein evolution on the viral replication competence and virulence.Emerging microbes & infections · 2022Article
- Biological Characterization of Yellow Fever Viruses Isolated From Non-human Primates in Brazil With Distinct Genomic Landscapes.Frontiers in microbiology · 2022Article
- Construction of an infectious clone of Zika virus stably expressing an EGFP marker in a eukaryotic expression system.Virology journal · 2021Article
- Compartmentalized replication organelle of flavivirus at the ER and the factors involved.Cellular and molecular life sciences : CMLS · 2021Review
- Rapid Construction of an Infectious Clone of the Zika Virus, Strain ZKC2.Frontiers in microbiology · 2021Article
- Recovery of Synthetic Zika Virus Based on Rio-U1 Isolate Using a Genetically Stable Two Plasmid System and cDNA Amplification.Frontiers in microbiology · 2021Article
- Identification of novel mutations in SARS-COV-2 isolates from Turkey.Archives of virology · 2020Article
- Zika Virus-Encoded NS2A and NS4A Strongly Downregulate NF-κB Promoter Activity.Journal of microbiology and biotechnology · 2020Article
- Single Amino Acid Mutations Affect Zika Virus Replication In Vitro and Virulence In Vivo.Viruses · 2020Article
- An overview of the current medical literature on Zika virus.Biophysical reviews · 2020Article
- Article
- Identification of Inhibitors of ZIKV Replication.Viruses · 2020Article
- Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2020Article
- Development, Characterization, and Application of Two Reporter-Expressing Recombinant Zika Viruses.Viruses · 2020Article
- In vivo rescue of recombinant Zika virus from an infectious cDNA clone and its implications in vaccine development.Scientific reports · 2020Article
- A natural polymorphism in Zika virus NS2A protein responsible of virulence in mice.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The recent outbreaks of Zika virus (ZIKV), its association with Guillain⁻Barré syndrome and fetal abnormalities, and the lack of approved vaccines and antivirals, highlight the importance of developing countermeasures to combat ZIKV disease. In this respect, infectious clones constitute excellent tools to accomplish these goals. However, flavivirus infectious clones are often difficult to work with due to the toxicity of some flavivirus sequences in bacteria. To bypass this problem, several alternative approaches have been applied for the generation of ZIKV clones including, among others, in vitro ligation, insertions of introns and using infectious subgenomic amplicons. Here, we report a simple and novel DNA-launched approach based on the use of a bacterial artificial chromosome (BAC) to generate a cDNA clone of Rio Grande do Norte Natal ZIKV strain. The sequence was identified from the brain tissue of an aborted fetus with microcephaly. The BAC clone was fully stable in bacteria and the infectious virus was efficiently recovered in Vero cells through direct delivery of the cDNA clone. The rescued virus yielded high titers in Vero cells and was pathogenic in a validated mouse model (A129 mice) of ZIKV infection. Furthermore, using this infectious clone we have generated a mutant ZIKV containing a single amino acid substitution (A175V) in the NS2A protein that presented reduced viral RNA synthesis in cell cultures, was highly attenuated in vivo and induced fully protection against a lethal challenge with ZIKV wild-type. This BAC approach provides a stable and reliable reverse genetic system for ZIKV that will help to identify viral determinants of virulence and facilitate the development of vaccine and therapeutic strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.