Genetic interaction between NS4A and NS4B for replication of Japanese encephalitis virus.

　　Li XD, Ye HQ, Deng CL, Liu SQ, Zhang HL, Shang BD, Shi PY, Yuan ZM, Zhang B.

  　J Gen Virol. 2015 Jan 9. pii: vir.0.000044. doi: 10.1099/vir.0.000044.

　　Abstract

　　Flavivirus NS4A and NS4B are important membrane proteins for viral replication that are assumed to serve as the scaffold for the formation of replication complexes (RCs). We previously demonstrated that a single Lys-to-Arg mutation at position 79 in NS4A protein (NS4A-K79R) significantly impaired Japanese encephalitis virus (JEV) replication. In this study, the mutant virus was subject to genetic selection to search for the potential interaction between NS4A and other viral components. Sequencing of the recovered viruses revealed that, besides a A97E change in NS4A protein itself, a Y3N compensatory mutation located in NS4B protein had emerged from independent selections. Mutagenesis analysis, using a genome-length RNA and a replicon of JEV, demonstrated that both adaptive mutations restored greatly the replication defect caused by NS4A-K79R. Our results, for the first time, clearly showed the genetic interaction between NS4A and NS4B although the mechanism underlying their interaction is unknown.

　　http://www.ncbi.nlm.nih.gov/pubmed/25575708