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

Xiao Dan Li, Han Qing Ye, Cheng Lin Deng, Si Qing Liu, Hong Lei Zhang, Bao Di Shang, Pei Yong Shi, Zhi Ming Yuan, Bo Zhang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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. We previously demonstrated that a single Lys-to-Arg mutation at position 79 in NS4A (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, in addition to an A97E change in NS4A itself, a Y3N compensatory mutation located in NS4B had emerged from independent selections. Mutagenesis analysis, using a genome-length RNA and a replicon of JEV, demonstrated that both adaptive mutations greatly restored the replication defect caused by NS4A-K79R. Our results, for the first time to our knowledge, clearly showed the genetic interaction between NS4A and NS4B, although the mechanism underlying their interaction is unknown.

Original languageEnglish (US)
Pages (from-to)1264-1275
Number of pages12
JournalJournal of General Virology
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Virology


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