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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
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Summary
This summary is machine-generated.

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.

Keywords:
Cedar virusHendra virusNipah virusantibodychimerahenipavirusreverse geneticsserumvaccinevirus neutralizationvirus-host cell interaction

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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.