Targeted cleavage site mutations in the Gn precursor enable efficient generation of replication-competent rVSV-based surrogates for emerging nairoviruses - PubMed
2 hours ago
- #neutralization
- #nairovirus
- #rVSV
- Orthonairoviruses are emerging tick-borne viruses, including Crimean Congo hemorrhagic fever virus (CCHFV), requiring high-level containment.
- Recombinant vesicular stomatitis virus (rVSV) systems are promising for vaccines and neutralization studies but face challenges in efficiently expressing nairovirus glycoproteins.
- Cleavage of nairovirus glycoprotein precursor (GPC) by host protease SKI-1/S1P is needed for mature Gn, with adaptive mutations observed during rVSV-CCHFV rescue.
- Targeted mutation of the SKI-1 cleavage site, resulting in uncleaved PreGn, combined with Gc tail truncation, improved rVSV-CCHFV rescue efficiency for two distinct strains.
- For Hazara virus (HAZV) and Yezo virus (YEZV), intact cleavage sites allowed efficient rVSV rescue, while mutations reduced replication, showing virus-specific requirements.
- rVSV-CCHFV provided reliable neutralization assays comparable to authentic CCHFV under BSL-4, using human convalescent and animal sera.
- Low cross-neutralizing activity was observed between CCHF-positive sera and VSV-HAZV.
- The findings enable generation of replication-competent rVSV vectors for nairovirus studies in lower containment facilities.