Functional divergence of NSs protein in Bhanja virus affects interferon antagonism and viral fitness
Researchers developed a reverse genetics platform for Bhanja virus (BHAV), a tick-borne virus with neuroinvasive capacity, and characterized how variations in its NSs protein affect interferon suppression. The NSs protein shows substantial amino acid divergence across geographic isolates, with African and European strains exhibiting stronger interferon antagonism than the prototype strain. These findings establish tools for studying BHAV and demonstrate how natural protein variations modulate immune evasion while maintaining an overall attenuated disease phenotype.
Scientists created a reverse genetics system for Bhanja virus by combining virion RNA sequencing with terminal untranslated region mapping, enabling systematic investigation of viral determinants. Testing in mammalian and arthropod cell lines revealed that interferon competence is critical for viral replication in mammalian cells. The study identified substantial amino acid divergence in the NSs protein—the primary innate immune antagonist—across geographically distinct BHAV isolates, despite higher conservation of other viral proteins. Recombinant viruses expressing NSs from African (ibAr2709) and European (R1819) isolates showed enhanced capacity to suppress interferon-beta induction compared to the prototype IG690 strain, correlating with increased viral protein accumulation. Mechanistic analysis revealed that BHAV NSs proteins inhibit interferon induction upstream of IRF3 through selective inhibition of TBK1 phosphorylation, though with weaker downstream interferon signaling antagonism than highly pathogenic bandaviruses like SFTSV. In vivo studies using interferon receptor-deficient mice confirmed that NSs sequence variation influences viral replication in splenic tissue without substantially altering overall disease severity.
What's missing
The study does not discuss potential clinical implications for human infection or disease severity in natural settings, nor does it address whether these NSs variations might affect vaccine or therapeutic development strategies.
What different sources said
- bioRxivCenter
Functional divergence of the NSs protein defines interferon antagonism and viral fitness across Bhanja virus lineages.
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