NS2B/NS3 mutations enhance the infectivity of genotype I Japanese encephalitis virus in amplifying hosts

• DOI: 10.1371/journal.ppat.1007992
• Publication Date: 2019-08-05T17:34:59Z
• Authors: Yi-Chin Fan; Jian-Jong Liang; Jo-Mei Chen; Jen-Wei Lin; Yi-Ying Chen; Kuan-Hsuan Su; Chang-Chi Lin; Wu-Chun Tu; Ming-Tang Chiou; Shan-Chia Ou; Gwong-Jen J. Chang; Yi-Ling Lin; Shyan-Song Chiou
• Keywords: NS3; Infectivity; Recombinant virus

Genotype I (GI) virus has replaced genotype III (GIII) as the dominant Japanese encephalitis (JEV) in epidemic area of Asia. The mechanism underlying replacement remains unclear. Therefore, we focused our current study on investigating roles mosquito vector and amplifying host(s) JEV by comparing replication ability GI GIII viruses. viruses had similar infection rates replicated to viral titers after blood meal feedings Culex tritaeniorhynchus. However, yielded a higher titer host-derived cells, especially at an elevated temperature, produced earlier viremia experimentally inoculated pigs, ducklings, young chickens. Subsequently identified amplification advantage genetic determinants from utilizing chimeric recombinant JEVs (rJEVs). Compared (rGIII virus), observed that both rJEVs encoding virus-derived NS1-3 genes supported hosts. was lost introduction single substitution mutation (NS2B-L99V, NS3-S78A, or NS3-D177E). In addition, gain-of-function assay further elucidated rGIII NS2B-V99L/NS3-A78S/E177E substitutions re-gained enhanced ability. Thus, conclude pigs poultry is result three critical NS2B/NS3 substitutions. This may lead more efficient transmission than host-mosquito cycle.