Wan Y
Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells
Dengue (DENV) and Zika (ZIKV) viruses are important human pathogens belonging to the Flaviviridae family of RNA viruses. DENV is known to infect around 390 million people around the world annually [1], while ZIKV causes numerous diseases including microcephaly in infants [2]. Currently, limited treatments and vaccines are available and novel strategies and targets are urgently needed to develop therapeutics to treat these diseases. To achieve this, it is important to understand host factors and how they interact with DENV and ZIKV genomes during the viral life cycle.
ReadFlavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes
The mosquito-borne flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have established themselves as major human pathogens. Live attenuated vaccines are seen as the most effective method for preventing flavivirus infection. Flavivirus genome recoding has emerged as a next-generation vaccine development method that acts by rewriting the flavivirus genome. Previous flavivirus genome recoding attempts were based on deoptimising the flavivirus genome. However, these deoptimised flaviviruses were found to be attenuated in a species dependent manner. For example, deoptimised DENV and ZIKV did not demonstrate attenuation in mosquito cells or mosquito animal models, which is undesirable because these mosquito-borne flaviviruses should be attenuated in their mosquito vector to prevent vaccine escape. To overcome these limitations, we adopted a flavivirus genome recoding approach based on the contrary approach of optimising the flavivirus genome and applied it to DENV2 and ZIKV. We found that this genome recoding approach of codon optimisation could confer attenuation in both mouse and mosquito animal models. This indicates that our flavivirus genome recoding approach may be used as a reliable method to construct attenuated vaccine backbones for the mosquito-borne-flaviviruses in general.
ReadDengue Virus Capsid Protein Facilitates Genome Compaction and Packaging
Keywords: dengue; RNA structure; RNA–protein interactions; virus packaging
ReadComprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions
SARS-CoV-2 is a major threat to global health. Here, we investigate the RNA structure and RNA-RNA interactions of wildtype (WT) and a mutant (Δ382) SARS-CoV-2 in cells using Illumina and Nanopore platforms. We identify twelve potentially functional structural elements within the SARS-CoV-2 genome, observe that subgenomic RNAs can form different structures, and that WT and Δ382 virus genomes fold differently.
ReadA novel method for the capture-based purification of whole viral native RNA genomes
Current technologies for targeted characterization and manipulation of viral RNA primarily involve amplification or ultracentrifugation with isopycnic gradients of viral particles to decrease host RNA background. The former strategy is non-compatible for characterizing properties innate to RNA strands such as secondary structure, RNA-RNA interactions, and also for nanopore direct RNA sequencing involving the sequencing of native RNA strands.
ReadStructure mapping of dengue and Zika viruses reveals functional long-range interactions
Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates.
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