Yellow fever Japanese encephalitis chimeric viruses: Construction and biological properties

A system has been developed for generating chimeric yellow fever/Japanese e ncephalitis (YF/JE) viruses from cDNA templates encoding the structural pro teins prM and E of JE virus within the backbone of a molecular clone of the YF17D strain. Chimeric viruses incorporating the proteins of two JE strain s, SA(14)-14-2 (human vaccine strain) and JE Nakayama (JE-N [virulent mouse brain-passaged strain]), were studied in cell culture and laboratory mice. The JE envelope protein (E) retained antigenic and biological properties w hen expressed with its prM protein together with the YF capsid; however, vi able chimeric viruses incorporating the entire JE structural region (C-prM- E) could not be obtained. YF/JE(prM-E) chimeric viruses grew efficiently in cells of vertebrate or mosquito origin compared to the parental viruses. T he YF/JE SA(14)-14-2 virus was unable to kill young adult mice by intracere bral challenge, even at doses of 10(6) PFU, In contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled parental YF virus rather tha n JE-N, Ten predicted amino acid differences distinguish the JE E proteins of the two chimeric viruses, therefore implicating one or more residues as virus-specific determinants of mouse neuroviruleuce in this chimeric system . This study indicates the feasibility of expressing protective antigens of JE virus in the context of a live, attenuated flavivirus vaccine strain (Y F17D) and also establishes a genetic system for investigating the molecular basis for neurovirulence determinants encoded within the JE E protein.