Fitness adaptations of Japanese encephalitis virus in pigs following vector-free serial passaging.

Autor: Marti A; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland., Nater A; Interfaculty Bioinformatics Unit (IBU) and Swiss Institute of Bioinformatics (SIB), University of Bern, Bern, Switzerland., Pego Magalhaes J; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Almeida L; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Lewandowska M; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland., Liniger M; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Ruggli N; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Grau-Roma L; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.; Institute of Animal Pathology, COMPATH, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Brito F; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Alnaji FG; A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Vignuzzi M; A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.; Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., García-Nicolás O; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Summerfield A; Institute of Virology and Immunology IVI, Mittelhäusern, Switzerland.; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Aug 26; Vol. 20 (8), pp. e1012059. Date of Electronic Publication: 2024 Aug 26 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012059
Abstrakt: Japanese encephalitis virus (JEV) is a zoonotic mosquito-transmitted Flavivirus circulating in birds and pigs. In humans, JEV can cause severe viral encephalitis with high mortality. Considering that vector-free direct virus transmission was observed in experimentally infected pigs, JEV introduction into an immunologically naïve pig population could result in a series of direct transmissions disrupting the alternating host cycling between vertebrates and mosquitoes. To assess the potential consequences of such a realistic scenario, we passaged JEV ten times in pigs. This resulted in higher in vivo viral replication, increased shedding, and stronger innate immune responses in pigs. Nevertheless, the viral tissue tropism remained similar, and frequency of direct transmission was not enhanced. Next generation sequencing showed single nucleotide deviations in 10% of the genome during passaging. In total, 25 point mutations were selected to reach a frequency of at least 35% in one of the passages. From these, six mutations resulted in amino acid changes located in the precursor of membrane, the envelope, the non-structural 3 and the non-structural 5 proteins. In a competition experiment with two lines of passaging, the mutation M374L in the envelope protein and N275D in the non-structural protein 5 showed a fitness advantage in pigs. Altogether, the interruption of the alternating host cycle of JEV caused a prominent selection of viral quasispecies as well as selection of de novo mutations associated with fitness gains in pigs, albeit without enhancing direct transmission frequency.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Marti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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