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

• DOI: 10.1371/journal.ppat.1012059
• Publication Date: 2024-08-26T20:59:48Z
• Authors: Andrea Marti; Alexander Nater; Jenny Pego Magalhaes; Lea Almeida; Marta Lewandowska; Matthias Liniger; Nicolas Ruggli; Llorenç Grau-Roma; Francisco Brito; Fadi G. Alnaji; Marco Vignuzzi; Obdulio García-Ni...; Artur Summerfield
• Keywords: Viral quasispecies; Flavivirus; Tissue tropism; Serial passage

Japanese encephalitis virus (JEV) is a zoonotic mosquito-transmitted Flavivirus circulating in birds and pigs. In humans, JEV can cause severe viral with high mortality. Considering that vector-free direct transmission was observed experimentally infected pigs, introduction into an immunologically naïve pig population could result series of transmissions disrupting the alternating host cycling between vertebrates mosquitoes. To assess potential consequences such realistic scenario, we passaged ten times This resulted higher vivo replication, increased shedding, stronger innate immune responses Nevertheless, tissue tropism remained similar, frequency not enhanced. Next generation sequencing showed single nucleotide deviations 10% genome during passaging. total, 25 point mutations were selected to reach at least 35% one passages. From these, six amino acid changes located precursor membrane, envelope, non-structural 3 5 proteins. competition experiment two lines passaging, mutation M374L envelope protein N275D fitness advantage Altogether, interruption cycle caused prominent selection quasispecies as well de novo associated gains albeit without enhancing frequency.