JE Nakayama/JE SA14-14-2 virus structural region intertypic viruses: biological properties in the mouse model of neuroinvasive disease.

Abstract

A molecular clone of Japanese encephalitis (JE) virus Nakayama strain was used to create intertypic viruses containing either the 5'-C-prM-E or the prM-E region of the attenuated JE SA14-14-2 virus in the JE Nakayama background. These two intertypic JE viruses, JE-X/5'CprME(S) and JE-X/prME(S), respectively, generally resembled the parental JE virus in cell culture properties. Similar to virus derived from the JE Nakayama molecular clone (JE-XJN), JE-X/prME(S) was highly neuroinvasive and neurovirulent for young adult mice, whereas JE-X/5'CprME(S) was attenuated for neuroinvasiveness and only partially attenuated for neurovirulence. Immunization of young mice with JE-X/5'CprME(S) virus elicited neutralizing antibodies against JE Nakayama virus and conferred protection against encephalitis following challenge with JE Nakayama virus. The sequence of the JE-X/5'CprME(S) virus differed from that of JE-X/prME(S) virus at two nucleotides in the 5' UTR, 3 amino acid positions in the capsid protein, 4 positions in the prM protein and 1 in the envelope protein. For JE-X/prME(S) virus, the 4 differences in prM and the single substitution in the envelope represented reversions to the sequence of JE Nakayama virus. Overall, this study reveals that molecular determinants associated with the prM-E region of the attenuated JE SA14-14-2 virus are insufficient by themselves to confer an attenuation phenotype upon JE Nakayama virus. This suggests a role for determinants in the 5' UTR and/or the capsid protein of the JE SA 14-14-2 virus genome in influencing the virulence properties of the JE Nakayama virus in the mouse model.

• Authors: Thomas J Chambers, Deborah A Droll, Xiaoshan Jiang, William S M Wold, Janice A Nickells
• Journal: Virology (Virology) Vol. 366 Issue 1 Pg. 51-61 (Sep 15 2007) ISSN: 0042-6822 [Print] United States
• PMID: 17521693 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Viral

Topics

• Animals
• Base Sequence
• Cloning, Molecular
• DNA, Viral (genetics)
• Disease Models, Animal
• Encephalitis Virus, Japanese (classification, genetics, pathogenicity)
• Encephalitis, Japanese (physiopathology)
• Genome, Viral
• Mice
• Nervous System Diseases (pathology, virology)
• Neurons (pathology, virology)
• Virulence