A Recombinant Chimeric Cedar Virus-Based Surrogate Neutralization Assay Platform for Pathogenic Henipaviruses
Author:
Amaya Moushimi1, Yin Randy12, Yan Lianying12, Borisevich Viktoriya34, Adhikari Bishwo N.56ORCID, Bennett Andrew67, Malagon Francisco67, Cer Regina Z.5, Bishop-Lilly Kimberly A.5ORCID, Dimitrov Antony S.12ORCID, Cross Robert W.34, Geisbert Thomas W.34ORCID, Broder Christopher C.1ORCID
Affiliation:
1. Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA 2. Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20814, USA 3. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA 4. Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA 5. Genomics and Bioinformatics Department, Biological Defense Research Directorate, Naval Medical Research Command–Frederick, Fort Detrick, Frederick, MD 21702, USA 6. Defense Threat Reduction Agency, Fort Belvoir, VA 22060, USA 7. Leidos, Inc., Reston, VA 20190, USA
Abstract
The henipaviruses, Nipah virus (NiV), and Hendra virus (HeV) can cause fatal diseases in humans and animals, whereas Cedar virus is a nonpathogenic henipavirus. Here, using a recombinant Cedar virus (rCedV) reverse genetics platform, the fusion (F) and attachment (G) glycoprotein genes of rCedV were replaced with those of NiV-Bangladesh (NiV-B) or HeV, generating replication-competent chimeric viruses (rCedV-NiV-B and rCedV-HeV), both with and without green fluorescent protein (GFP) or luciferase protein genes. The rCedV chimeras induced a Type I interferon response and utilized only ephrin-B2 and ephrin-B3 as entry receptors compared to rCedV. The neutralizing potencies of well-characterized cross-reactive NiV/HeV F and G specific monoclonal antibodies against rCedV-NiV-B-GFP and rCedV-HeV-GFP highly correlated with measurements obtained using authentic NiV-B and HeV when tested in parallel by plaque reduction neutralization tests (PRNT). A rapid, high-throughput, and quantitative fluorescence reduction neutralization test (FRNT) using the GFP-encoding chimeras was established, and monoclonal antibody neutralization data derived by FRNT highly correlated with data derived by PRNT. The FRNT assay could also measure serum neutralization titers from henipavirus G glycoprotein immunized animals. These rCedV chimeras are an authentic henipavirus-based surrogate neutralization assay that is rapid, cost-effective, and can be utilized outside high containment.
Funder
National Institutes of Health Coalition for Epidemic Preparedness Innovations NIAID/NIH Naval Medical Research Center
Subject
Virology,Infectious Diseases
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