A Recombinant Chimeric Cedar Virus-Based Surrogate Neutralization Assay Platform for Pathogenic Henipaviruses
Moushimi Amaya1, Randy Yin1,2, Lianying Yan1,2
1Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA.
Viruses
|May 27, 2023
Summary
Researchers developed novel chimeric henipaviruses using Cedar virus as a backbone. These engineered viruses serve as a safe and effective surrogate for Nipah virus and Hendra virus neutralization assays, enabling high-throughput testing outside high containment.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses causing severe disease in humans and animals.
- Cedar virus (CedV) is a nonpathogenic henipavirus, offering a potential platform for developing safer research tools.
- Existing neutralization assays for henipaviruses often require high containment facilities, limiting accessibility and throughput.
Purpose of the Study:
- To create replication-competent chimeric heniviruses using a recombinant Cedar virus (rCedV) reverse genetics system.
- To establish a rapid, high-throughput, and quantitative surrogate neutralization assay for NiV and HeV.
- To evaluate the utility of these chimeric viruses for testing monoclonal antibody and serum neutralization.
Main Methods:
- Replaced fusion (F) and attachment (G) glycoprotein genes of rCedV with those from NiV-Bangladesh (NiV-B) or HeV.
- Generated chimeric viruses (rCedV-NiV-B and rCedV-HeV) with and without reporter genes (GFP or luciferase).
- Established a fluorescence reduction neutralization test (FRNT) using GFP-encoding chimeras and compared results with plaque reduction neutralization tests (PRNT).
Main Results:
- The rCedV chimeras induced a Type I interferon response and used ephrin-B2/B3 as entry receptors, similar to pathogenic henipaviruses.
- Neutralization potencies of monoclonal antibodies against chimeric viruses highly correlated with those against authentic NiV-B and HeV.
- The developed FRNT assay demonstrated high correlation with PRNT and could measure serum neutralization titers from immunized animals.
Conclusions:
- Recombinant Cedar virus chimeras expressing NiV-B or HeV glycoproteins provide an authentic henipavirus-based surrogate neutralization assay.
- The FRNT assay is rapid, cost-effective, and suitable for use outside high containment, facilitating broader henipavirus research.
- These tools can aid in the development and evaluation of therapeutic antibodies and vaccines against Nipah and Hendra viruses.
Keywords:
Cedar virusHendra virusNipah virusantibodychimerahenipavirusreverse geneticsserumvaccinevirus neutralizationvirus-host cell interaction
