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Research Project: Viral Ecology of Henipaviruses in Endemic Settings and Intervention Strategies to Prevent their Spread to Domestic Animals

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Title: Optimization of Bangladesh and Malaysian genotype recombinant reporter nipah viruses for in vitro antiviral screening and in vivo disease modeling

Author
item LO, MICHAEL - Centers For Disease Control And Prevention (CDC) - United States
item JAIN, SHILPI - Emory University
item DAVIS, KATHERINE - Oak Ridge Institute For Science And Education (ORISE)
item SORVILLO, TERESA - Centers For Disease Control And Prevention (CDC) - United States
item WELCH, STEPHEN - Centers For Disease Control And Prevention (CDC) - United States
item COLEMAN-MCCRAY, JOANN - Centers For Disease Control And Prevention (CDC) - United States
item CHATTERJEE, PAYEL - Centers For Disease Control And Prevention (CDC) - United States
item HOTARD, ANNE - Centers For Disease Control And Prevention (CDC) - United States
item O'NEAL, TROY - Centers For Disease Control And Prevention (CDC) - United States
item FLINT, MIKE - Centers For Disease Control And Prevention (CDC) - United States
item AI, HUIWANG - University Of Virginia School Of Medicine
item ALBARINO, CESAR - Centers For Disease Control And Prevention (CDC) - United States
item SPENGLER, JESSICA - Centers For Disease Control And Prevention (CDC) - United States
item MONTGOMERY, JOEL - Centers For Disease Control And Prevention (CDC) - United States
item SPIROPOULOU, CHRISTINA - Centers For Disease Control And Prevention (CDC) - United States

Submitted to: Antiviral Research
Publication Type: Review Article
Publication Acceptance Date: 9/23/2024
Publication Date: 10/1/2024
Citation: Lo, M.K., Jain, S., Davis, K.A., Sorvillo, T.E., Welch, S.R., Coleman-Mccray, J.D., Chatterjee, P., Hotard, A.L., O'Neal, T., Flint, M., Ai, H., Albarino, C.G., Spengler, J.R., Montgomery, J.M., Spiropoulou, C.F. 2024. Optimization of Bangladesh and Malaysian genotype recombinant reporter nipah viruses for in vitro antiviral screening and in vivo disease modeling. Antiviral Research. 231. https://doi.org/10.1016/j.antiviral.2024.106013.
DOI: https://doi.org/10.1016/j.antiviral.2024.106013

Interpretive Summary: The paper describes the development of a virus that will express a green fluorescent protein as a tool to understand how the virus causes disease and to aid in the development of countermeasures. The expression of the green protein aids in the following of the virus and makes it easier to detect the absence or presence of the virus.

Technical Abstract: Nipah virus (NiV) causes near-annual outbreaks of fatal encephalitis and respiratory disease in South Asia with a high mortality rate (~70%). Since there are no approved therapeutics for NiV disease in humans, the WHO has designated NiV and henipaviral diseases priority pathogens for research and development. We generated a new recombinant green fluorescent reporter NiV of the circulating Bangladesh genotype (rNiV-B-ZsG) and optimized it alongside our previously generated Malaysian genotype reporter counterpart (rNiV-M-ZsG) for antiviral screening in primary-like human respiratory cell types. Validating our platform for rNiV-B-ZsG with a synthetic compound library directed against viral RNA-dependent RNA polymerases, we identified a hit compound and confirmed its sub-micromolar activity against wild-type NiV, green fluorescent reporter, and the newly constructed bioluminescent red fluorescent double reporter (rNiV-B-BREP) NiV. We furthermore demonstrated that rNiV-B-ZsG and rNiV-B-BREP viruses showed pathogenicity comparable to wild-type NiV-B in the Syrian golden hamster model of disease, supporting additional use of these tools for both pathogenesis and advanced pre-clinical studies in vivo.