A Single Amino Acid Substitution in the M Protein Attenuates Japanese Encephalitis Virus in Mammalian Hosts

• DOI: 10.1128/jvi.01176-15
• Publication Date: 2015-12-11T12:54:04Z
• Authors: Mélissanne de Wis...; Cécile Khou; Marie-Pascale Fre...; Philippe Desprès; Nathalie Pardigon
• Keywords: Flavivirus; Reverse Genetics

Japanese encephalitis virus (JEV) membrane (M) protein plays important structural roles in the processes of fusion and maturation progeny during cellular infection. The M is anchored viral membrane, its ectodomain composed a flexible N-terminal loop perimembrane helix. In this study, we performed site-directed mutagenesis on residue 36 JEV showed that resulting mutation had little or no effect entry process but greatly affected assembly mammalian cells. Interestingly, mutant host-dependent phenotype could develop wild-type infection insect Experiments infectious as well virus-like particle (VLP) system indicate expresses proteins fails to form particles Using mouse model for pathogenesis, conferred complete attenuation vivo. production neutralizing antibodies challenged mice was indicative immunogenicity Together, our results introduction single protein, while being tolerated cells, strongly impacts hosts.JEV mosquito-transmitted flavivirus medically pathogen Asia. thought be accommodating rearrangements undergone by virion may play additional cycle. present show sole impairs cycle hosts not mosquito This finding highlights differences pathways among hosts. Moreover, indicated completely attenuated triggered strong immune response JEV, thus providing new insights further development vaccines.