NS1’, a newly re-identified protein in flavivirus, plays a role as caspase substrate
Japanese encephalitis virus （JEV） is a flavivirus with a complex life cycle involving mosquito vectors that mainly target birds and pigs, and causes severe encephalitis in children in Asia.
Under supervision of Prof. Vincent Deubel, SUN Jin, Ph.D student at Institut Pasteur of Shanghai, Chinese Academy of Sciences（IPS-CAS), recently confirmed the need of the pseudoknot structure for NS1' synthesis in JEV for the first time and found NS1' to be absent from the JEV SA14-14-2 vaccine strain, resulting from a single nucleotide silent mutation in the pseudoknot. This work entitled "Japanese encephalitis virus NS1' protein depends on pseudoknot secondary structure and is cleaved by caspase during virus infection and cell apoptosis" was published in the latest issue of Microbes and Infection (2012).
Neurotropic flaviviruses of the JEV serogroup have a particular characteristic of expressing a unique nonstructural NS1' protein, which is a prolongation of NS1 at the C terminus by 52 amino acids derived from a pseudoknot-driven -1 translation frameshift. It’s been reported that protein NS1' was associated with West Nile Virus neuro-invasiveness, however, seldom study was carried out on this newly re-identified protein.
With molecular biological method, SUN Jin confirmed frame-shift mechanism for NS1' synthesis in JEV for the first time, and prepared antibodies against NS1’ based on frame-shift peptide. Using this antibody, researchers found NS1' to be absent from the JEV SA14-14-2 vaccine strain, resulting from a single nucleotide silent mutation in the pseudoknot. This mutation could be one candidate for attenuation markers in vaccine virus. Coincidently, a unique feature of intracellular NS1' was found to be cleaved by caspases during virus induced apoptosis. Upon JEV infection, caspases in cells is activated, and subsequently cleaves NS1’ C-terminal appendix after 381th residues. The unique behavior as caspase substrate may confer to NS1' a role in modulating host cell response to JEV infection.
This study has contributed to the further works on illustrating mechanism of flavivirus neuro-invassiveness, and host response upon infection.
This work was supported by Shanghai Pasteur Health Research Foundation (SPHRF) and Innovation fund of Chinese Academy of Sciences.
Fig. 1. JEV NS1' expression in SA14-14-2–infected BHK-21 cells is abrogated by a single nucleotide mutation (E22E’) in NS2A.