Chimeric Japanese encephalitis virus/dengue 2 virus infectious clone: biological properties, immunogenicity and protection against dengue encephalitis in mice.
A molecular clone of Japanese encephalitis virus (JE virus) was derived from the JE virus Nakayama strain and used to produce infectious JE virus in cell culture. The engineered JE virus resembled the parental JE virus in cell-culture properties and was related closely to other JE virus strains based on nucleotide sequence analysis. The JE virus clone was used as a genetic background for construction of a chimeric virus containing the structural proteins prM and E of Dengue virus, serotype 2. The chimeric JE/dengue 2 virus generated authentic dengue 2 structural proteins as assessed by immunoassays for the dengue E protein. It exhibited a small plaque size and less efficient growth in various cell lines than the parental JE virus. JE/dengue 2 virus was non-neuroinvasive for young adult mice, but displayed partial neurovirulence at doses up to 4 log p.f.u. given intracerebrally. Immunization of 3-week-old mice with JE/dengue 2 virus yielded neutralizing-antibody titres against dengue 2 virus and conferred protection against dengue encephalitis caused by neuroadapted dengue 2 virus. A rise in post-challenge neutralizing-antibody titres against dengue 2 virus in surviving mice suggests that immunization is associated with establishment of a memory antibody response in this model. This study demonstrates the capacity of JE virus to serve as a vector for expression of heterologous flavivirus structural proteins. Similar to previous studies with other chimeric flaviviruses, this approach may be useful as a genetic system for engineering experimental vaccines against Dengue virus and other medically important flaviviruses.
Chambers
Thomas J
TJ
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, 1402 South Grand Avenue, St Louis, MO 63104, USA.
Jiang
Xiaoshan
X
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, 1402 South Grand Avenue, St Louis, MO 63104, USA.
Droll
Deborah A
DA
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, 1402 South Grand Avenue, St Louis, MO 63104, USA.
Liang
Yan
Y
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, 1402 South Grand Avenue, St Louis, MO 63104, USA.
Wold
William S M
WSM
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, 1402 South Grand Avenue, St Louis, MO 63104, USA.
Nickells
Janice
J
Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, 1402 South Grand Avenue, St Louis, MO 63104, USA.
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002460:Cell Line; D003715:Dengue / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000235:genetics*; D018792:Encephalitis, Viral / Q000276:immunology* / Q000517:prevention & control*; D005822:Genetic Vectors; D007114:Immunization; D051379:Mice; D008813:Mice, Inbred ICR; D009500:Neutralization Tests; D016865:Reassortant Viruses / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D012703:Serotyping; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis / Q000276:immunology; D014774:Virulence
D000914:Antibodies, Viral; C051821:E-glycoprotein, Dengue virus type 2; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C084187:prM protein, Dengue virus type 3