Host-virus molecular arms race: RNAi-mediated antiviral defense and viral suppressor of RNAi

RNA interference (RNAi) is a highly conserved post-transcriptional gene silencing (PTGS) mechanism widely presented in eukaryotes. During viral infection, double-stranded RNA viral replicative intermediate (vRI-dsRNA) derived from the viral genome is recognized and processed by Dicer to generate small interfering RNA (siRNA). The viral siRNA (vsiRNA) is subsequently loaded into the RNA-induced silencing complex (RISC), which targets and degrades viral RNAs to achieve antiviral immune response. During long-term evolution, viruses have evolved to counteract RNAi by encoding viral suppressors of RNAi (VSRs) through various strategies, thereby evading the immune clearance. Here we review how VSRs function as immune evasion factors against antiviral RNAi, along with their evolutionary significance in shaping both viral adaptation and host-pathogen co-evolution. We also discuss recent advancements and unresolved controversies regarding RNAi-mediated antiviral immunity in mammals. Finally, we provide a comprehensive analysis of emerging therapeutic strategies and vaccine designs that leverage the RNAi-VSR interaction mechanisms, while addressing their potential prospects and challenges in clinical translation.

• Publication year

  2025

• Venue

  Cell Insight

• Publication date

  2025-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.cellin.2025.100276PMID 40994739PMCID 12454879
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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