Optimization of Bangladesh and Malaysian genotype recombinant reporter Nipah viruses for in vitro antiviral screening and in vivo disease modeling.

Autor: Lo MK; Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: mko2@cdc.gov., Jain S; Emory National Primate Research Center, Emory Vaccine Center, Emory University, Atlanta, GA, USA., Davies KA; Centers for Disease Control and Prevention, Atlanta, GA, USA; U.S. Department of Agriculture, Agricultural Research Service, Zoonotic and Emerging Disease Research Unit, National Bio and Agro-Defense Facility, Manhattan, KS, USA., Sorvillo TE; Centers for Disease Control and Prevention, Atlanta, GA, USA., Welch SR; Centers for Disease Control and Prevention, Atlanta, GA, USA., Coleman-McCray JD; Centers for Disease Control and Prevention, Atlanta, GA, USA., Chatterjee P; Centers for Disease Control and Prevention, Atlanta, GA, USA., Hotard AL; Centers for Disease Control and Prevention, Atlanta, GA, USA., O'Neal T; Centers for Disease Control and Prevention, Atlanta, GA, USA., Flint M; Centers for Disease Control and Prevention, Atlanta, GA, USA., Ai H; University of Virginia, School of Medicine, Charlottesville, VA, USA., Albariño CG; Centers for Disease Control and Prevention, Atlanta, GA, USA., Spengler JR; Centers for Disease Control and Prevention, Atlanta, GA, USA., Montgomery JM; Centers for Disease Control and Prevention, Atlanta, GA, USA., Spiropoulou CF; Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: ccs8@cdc.gov.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2024 Nov; Vol. 231, pp. 106013. Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1016/j.antiviral.2024.106013
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Published by Elsevier B.V.)
Databáze: MEDLINE
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