Live-attenuated flavivirus vaccines confer long-term protection against disease, but the design of attenuated flaviviruses does not follow a general approach. The non-coding, subgenomic flavivirus RNA (sfRNA) is produced by all flaviviruses and is an essential factor in viral pathogenesis and transmission. We argue that modulating sfRNA expression is a promising, universal strategy to finetune flavivirus attenuation for developing effective flavivirus vaccines of the future.
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http://dx.doi.org/10.1128/jvi.00100-23 | DOI Listing |
bioRxiv
December 2024
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Exoribonuclease-resistant RNAs (xrRNAs) are viral RNA structures that block degradation by cellular 5'-3' exoribonucleases to produce subgenomic viral RNAs during infection. Initially discovered in flaviviruses, xrRNAs have since been identified in wide range of RNA viruses, including those that infect plants. High sequence variability among viral xrRNAs raises questions about the shared molecular features that characterize this functional RNA class.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
PHIM Plant Health Institute, University of Montpellier, INRAE, CIRAD, IRD, Institute Agro, 34398 Montpellier, France.
The green peach aphid () is a generalist pest damaging crops and transmitting viral pathogens. Using Illumina sequencing of small (s)RNAs and poly(A)-enriched long RNAs, we analyzed aphid virome components, viral gene expression and antiviral RNA interference (RNAi) responses. Myzus persicae densovirus (family ), a single-stranded (ss)DNA virus persisting in the aphid population, produced 22 nucleotide sRNAs from both strands of the entire genome, including 5'- and 3'-inverted terminal repeats.
View Article and Find Full Text PDFElife
November 2024
Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Canada.
Zika virus (ZIKV) infection causes significant human disease that, with no approved treatment or vaccine, constitutes a major public health concern. Its life cycle entirely relies on the cytoplasmic fate of the viral RNA genome (vRNA) through a fine-tuned equilibrium between vRNA translation, replication, and packaging into new virions, all within virus-induced replication organelles (vROs). In this study, with an RNA interference (RNAi) mini-screening and subsequent functional characterization, we have identified insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a new host dependency factor that regulates vRNA synthesis.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Centre for Human Technologies, Istituto Italiano di Tecnologia, Via Enrico Melen, 83, Genova GE 16152, Italy.
Flaviviruses pose significant global health threats, infecting over 300 million people annually. Among their evasion strategies, the production of subgenomic flaviviral RNAs (sfRNAs) from the 3' UTR of viral genomes is particularly notable. Utilizing a comprehensive approach with the RAPID algorithm, we analyzed over 300,000 interactions between sfRNAs and human proteins derived from more than 8000 flavivirus genomes, including Dengue, Zika, Yellow Fever, West Nile, and Japanese Encephalitis viruses.
View Article and Find Full Text PDFJ Virol
November 2024
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
RNA interference (RNAi) plays an essential role in mosquito antiviral immunity, but it is not known whether viral small interfering RNA (siRNA) profiles differ between mosquito-borne and mosquito-specific viruses. A pan-Orthoflavivirus analysis in cells revealed that viral siRNAs were evenly distributed across the viral genome of most representatives of the genus. In contrast, siRNA production was biased toward the 3' untranslated region (UTR) of the genomes of classical insect-specific flaviviruses (cISF), which was most pronounced for Kamiti River virus (KRV), a virus with a unique, 1.
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