Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class Insecta) and ticks (class Arachnida). RNA interference (RNAi) is the major antiviral mechanism in arthropods against arboviruses. Unlike in mosquitoes, tick antiviral RNAi is not understood, although this information is important to compare arbovirus/host interactions in different classes of arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute proteins involved in RNAi and the response against tick-borne Langat virus (Flaviviridae) replication were identified and phylogenetic relationships characterized. Analysis of small RNAs in infected cells showed the production of virus-derived small interfering RNAs (viRNAs), which are key molecules of the antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than those from other arbovirus vectors and mapped at highest frequency to the termini of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick-borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick RNAi. Our results characterize the antiviral RNAi response in tick cells including phylogenetic analysis of genes encoding antiviral proteins, and viral interference with this pathway. This shows important differences in antiviral RNAi between the two major classes of arbovirus vectors, and our data broadens our understanding of arthropod antiviral RNAi.
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http://dx.doi.org/10.1093/nar/gku657 | DOI Listing |
Int 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 PDFInsect Mol Biol
December 2024
Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Biological Science Research Center, Southwest University, Chongqing, China.
Insect NF-κB-like factor, Relish, is activated by viral infection and induces the production of antiviral proteins. In this study, we performed a transcriptomic analysis of BmE cells expressing the active form of BmRelish (BmRelish) and identified BmVago-like as the most strongly-induced secreted-protein. Expression of BmVago-like was specifically triggered by Bombyx mori Nucleo Polyhedro Virus (BmNPV) infection and regulated by BmSTING-BmRelish pathway.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Germany.
Viruses of the class Bunyaviricetes are often transmitted by arthropods, including mosquitoes. The innate immune response in mosquitoes comprises several pathways, including sequence-specific degradation through RNA interference (RNAi). It is known that bunyavirus infections are targeted by the innate immune response in mosquitoes and derived cells; however, detailed information is often still missing.
View Article and Find Full Text PDFMol Ther
December 2024
State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan 430071, China; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. Electronic address:
Infections caused by coronaviruses are persistent threats to human health in recent decades, necessitating the development of innovative anti-coronaviral therapies. RNA interference (RNAi) is a conserved cell-intrinsic antiviral mechanism in diverse eukaryotic organisms, including mammals. To counteract, many viruses encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi, implying that targeting VSRs could be a promising strategy to develop antiviral therapies.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Alnylam Pharmaceuticals; Cambridge, MA 002142, USA.
RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral RNA. We identified potent lipophilic small interfering RNA (siRNA) conjugates targeting highly conserved regions of SARS-CoV-2 outside of the spike-encoding region capable of achieving ≥3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single siRNA approach.
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