A conserved in-frame stop codon acts as a multipotent defense mechanism in alphaviruses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42308287.
- Also identified by DOI 10.1126/sciadv.aee6015 and PMC identifier 13274604.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Most alphaviruses maintain an in-frame opal stop codon that interrupts their nonstructural polyprotein (nsP) ORF between nsP3 and nsP4 in both vertebrate and insect hosts. We show that the nsP3 opal stop codon confers a replicative advantage to Sindbis virus (SINV) in RNAi-competent <i>Aedes</i> cells and mosquitoes but not in RNAi-deficient cells or mosquitoes. Mutation of the opal stop codon delays processing of the viral nsP polyprotein, disrupts viral replication spherule integrity, and renders viral RNA susceptible to Dicer 2 cleavage, resulting in higher antiviral siRNA responses against SINV. Similarly, these defects caused by opal codon mutations lead to increased viral RNA detection and enhanced immune signaling in vertebrate cells. Thus, a single stop codon in alphaviruses mediates a multipotent viral strategy to evade innate immune defenses across diverse hosts.
Medical subject headings
- Sindbis Virus
- Codon, Terminator
- Alphavirus