Yellow Fever/Japanese Encephalitis Chimeric Viruses: Construction and Biological Properties

ABSTRACT A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins 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 strains, SA14-14-2 (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 when expressed with its prM protein together with the YF capsid; however, viable 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. The YF/JE SA14-14-2 virus was unable to kill young adult mice by intracerebral challenge, even at doses of 106 PFU. In contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled parental YF virus rather than 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 neurovirulence 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 (YF17D) and also establishes a genetic system for investigating the molecular basis for neurovirulence determinants encoded within the JE E protein.

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Yellow Fever Virus/Dengue-2 Virus and Yellow Fever Virus/Dengue-4 Virus Chimeras: Biological Characterization, Immunogenicity, and Protection against Dengue Encephalitis in the Mouse Model

Journal of Virology ◽

10.1128/jvi.77.6.3655-3668.2003 ◽

2003 ◽

Vol 77 (6) ◽

pp. 3655-3668 ◽

Cited By ~ 33

Author(s):

Thomas J. Chambers ◽

Yan Liang ◽

Deborah A. Droll ◽

Jacob J. Schlesinger ◽

Andrew D. Davidson ◽

...

Keyword(s):

Mouse Model ◽

Dengue Virus ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Fever Virus ◽

E Proteins ◽

Dengue Viruses ◽

Intracerebral Inoculation ◽

Intraperitoneal Route ◽

Chimeric Viruses

ABSTRACT Two yellow fever virus (YFV)/dengue virus chimeras which encode the prM and E proteins of either dengue virus serotype 2 (dengue-2 virus) or dengue-4 virus within the genome of the YFV 17D strain (YF5.2iv infectious clone) were constructed and characterized for their properties in cell culture and as experimental vaccines in mice. The prM and E proteins appeared to be properly processed and glycosylated, and in plaque reduction neutralization tests and other assays of antigenic specificity, the E proteins exhibited profiles which resembled those of the homologous dengue virus serotypes. Both chimeric viruses replicated in cell lines of vertebrate and mosquito origin to levels comparable to those of homologous dengue viruses but less efficiently than the YF5.2iv parent. YFV/dengue-4 virus, but not YFV/dengue-2 virus, was neurovirulent for 3-week-old mice by intracerebral inoculation; however, both viruses were attenuated when administered by the intraperitoneal route in mice of that age. Single-dose inoculation of either chimeric virus at a dose of 105 PFU by the intraperitoneal route induced detectable levels of neutralizing antibodies against the homologous dengue virus strains. Mice which had been immunized in this manner were fully protected from challenge with homologous neurovirulent dengue viruses by intracerebral inoculation compared to unimmunized mice. Protection was associated with significant increases in geometric mean titers of neutralizing antibody compared to those for unimmunized mice. These data indicate that YFV/dengue virus chimeras elicit antibodies which represent protective memory responses in the mouse model of dengue encephalitis. The levels of neurovirulence and immunogenicity of the chimeric viruses in mice correlate with the degree of adaptation of the dengue virus strain to mice. This study supports ongoing investigations concerning the use of this technology for development of a live attenuated viral vaccine against dengue viruses.

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Development of chimaeric West Nile virus attenuated vaccine candidate based on the Japanese encephalitis vaccine strain SA14-14-2

Journal of General Virology ◽

10.1099/vir.0.059436-0 ◽

2013 ◽

Vol 94 (12) ◽

pp. 2700-2709 ◽

Cited By ~ 12

Author(s):

Xiao-Feng Li ◽

Wei Zhao ◽

Fang Lin ◽

Qing Ye ◽

Hong-Jiang Wang ◽

...

Keyword(s):

West Nile Virus ◽

Japanese Encephalitis ◽

Vaccine Development ◽

Vaccine Candidate ◽

Genetic System ◽

Reverse Genetic System ◽

West Nile ◽

Protective Antigens ◽

Japanese Encephalitis Vaccine

Mosquito-borne flaviviruses include a large group of important human medical pathogens. Several chimaeric flaviviruses have been constructed, and show potential for vaccine development. Although Japanese encephalitis virus (JEV) live vaccine SA14-14-2 has been widely used with ideal safety and efficacy profiles, no chimaeric flavivirus based on the JEV vaccine has been described to date. Based on the reverse genetic system of the JEV vaccine SA14-14-2, a novel live chimaeric flavivirus carrying the protective antigens of West Nile virus (WNV) was constructed and recovered in this study. The resulting chimaera (ChinWNV) replicated efficiently in both mammalian and mosquito cells and possessed genetic stability after in vitro serial passaging. ChinWNV exhibited a small-plaque phenotype, and its replication was significantly restricted in mouse peripheral blood and brain compared with parental WNV. Importantly, ChinWNV was highly attenuated with regard to both neurovirulence and neuroinvasiveness in mice. Furthermore, a single ChinWNV immunization stimulated robust WNV-specific adaptive immune responses in mice, conferring significant protection against lethal WNV infection. Our results demonstrate that chimaeric flaviviruses based on the JEV vaccine can serve as a powerful platform for vaccine development, and that ChinWNV represents a potential WNV vaccine candidate that merits further development.

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Production of single-round infectious chimeric flaviviruses with DNA-based Japanese encephalitis virus replicon

Journal of General Virology ◽

10.1099/vir.0.058008-0 ◽

2014 ◽

Vol 95 (1) ◽

pp. 60-65 ◽

Cited By ~ 27

Author(s):

Ryosuke Suzuki ◽

Tomohiro Ishikawa ◽

Eiji Konishi ◽

Mami Matsuda ◽

Koichi Watashi ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Yellow Fever ◽

Japanese Encephalitis ◽

Life Cycles ◽

Encephalitis Virus ◽

Coding Region ◽

E Proteins ◽

Subgenomic Replicon ◽

Tick Borne Encephalitis Virus ◽

Diagnostic Applications

A method for rapid production of single-round infectious particles (SRIPs) of flavivirus would be useful for viral mutagenesis studies. Here, we established a DNA-based production system for SRIPs of flavivirus. We constructed a Japanese encephalitis virus (JEV) subgenomic replicon plasmid, which lacked the C-prM-E (capsid–pre-membrane–envelope) coding region, under the control of the cytomegalovirus promoter. When the JEV replicon plasmid was transiently co-transfected with a JEV C-prM-E expression plasmid into 293T cells, SRIPs were produced, indicating successful trans-complementation with JEV structural proteins. Equivalent production levels were observed when C and prM–E proteins were provided separately. Furthermore, dengue types 1–4, West Nile, yellow fever or tick-borne encephalitis virus prM-E proteins could be utilized for production of chimaeric flavivirus SRIPs, although the production was less efficient for dengue and yellow fever viruses. These results indicated that our plasmid-based system is suitable for investigating the life cycles of flaviviruses, diagnostic applications and development of safer vaccine candidates.

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ANTIGENIC ANALYSIS OF CERTAIN GROUP B ARTHROPOD-BORNE VIRUSES BY ANTIBODY ABSORPTION

Journal of Experimental Medicine ◽

10.1084/jem.111.1.21 ◽

1960 ◽

Vol 111 (1) ◽

pp. 21-32 ◽

Cited By ~ 43

Author(s):

D. H. Clarke

Keyword(s):

Yellow Fever ◽

Vaccine Strain ◽

Yellow Fever Virus ◽

Geographical Area ◽

Specific Antigen ◽

Antigenic Structure ◽

Antigenic Analysis ◽

West Nile ◽

Antibody Absorption ◽

Group B

A method for carrying out antibody absorption studies for antigenic analysis of group B arthropod-borne (arbor) viruses is described and examples of homologous and heterologous absorption curves are presented. Evidence that antigenic structure can be a stable property was obtained with three strains of West Nile virus isolated from different hosts in different countries over a period of years. Comparative studies with viruses of the Japanese B-St. Louis-West Nile subgroup indicate that each virus contains a completely specific antigen as well as one or more cross-reactive components. Strains of yellow fever virus isolated in America were shown to lack an antigen present in strains of African origin although no differences were found between isolates from the same geographical area. The attenuated 17 D vaccine strain of yellow fever was found to have acquired an additional antigen not present in the unadapted parent or in other strains tested. However, alteration in pathogenicity for man was not found to be necessarily attended by any antigenic modification, as shown by the antigenic identity of the French neurotropic vaccine strain with its pantropic parent.

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New data on distribution of invasive mosquito species in the Europe and in Russia

Disinfection affairs ◽

10.35411/2076-457x-2021-2-36-43 ◽

2021 ◽

pp. 36-43

Author(s):

Svetala Aleksandrovna Roslavtseva ◽

◽

Alla Iosifovna Frolova ◽

Mikhail Anatol’evich Alekseev ◽

◽

...

Keyword(s):

Global Warming ◽

Yellow Fever ◽

Japanese Encephalitis ◽

World Trade ◽

Mosquito Species ◽

Biological Characteristics ◽

Invasive Mosquito Species ◽

Invasive Mosquito

Literature on distribution of invasive mosquito species that are vectors of especially dangerous infections (dengue, Chikungunya, Zika, yellow fever, and Japanese encephalitis) in the Europe and Russia was briefly reviewed. Global warming of the climate as well as an increase in the volume of world trade and the biological characteristics of mosquitoes contribute to the widespread of these species on territories of many countries and continents

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Molecular analysis of yellow fever virus 17DD vaccine strain

Memórias do Instituto Oswaldo Cruz ◽

10.1590/s0074-02761991000200015 ◽

1991 ◽

Vol 86 (2) ◽

pp. 239-246 ◽

Cited By ~ 3

Author(s):

Paulo R. Post ◽

Claudia N. D. Santos ◽

Ricardo Carvalho ◽

Oscar S. Lopes ◽

Ricardo Galler

Keyword(s):

Yellow Fever ◽

Molecular Analysis ◽

Vaccine Strain ◽

Yellow Fever Virus ◽

Fever Virus

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Japanese encephalitis virus/yellow fever virus chimera is safe and confers full protection against yellow fever virus in intracerebrally challenged mice

Vaccine ◽

10.1016/j.vaccine.2018.03.038 ◽

2018 ◽

Vol 36 (18) ◽

pp. 2450-2455 ◽

Cited By ~ 3

Author(s):

Huiqiang Yang ◽

Huan Yang ◽

Zhushi Li ◽

Lina Liu ◽

Wei Wang ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Yellow Fever ◽

Japanese Encephalitis ◽

Yellow Fever Virus ◽

Encephalitis Virus ◽

Fever Virus ◽

Full Protection

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Immunogenicity, Genetic Stability, and Protective Efficacy of a Recombinant, Chimeric Yellow Fever-Japanese Encephalitis Virus (ChimeriVax-JE) as a Live, Attenuated Vaccine Candidate against Japanese Encephalitis

Virology ◽

10.1006/viro.1999.9695 ◽

1999 ◽

Vol 257 (2) ◽

pp. 363-372 ◽

Cited By ~ 123

Author(s):

F. Guirakhoo ◽

Z.-X. Zhang ◽

T.J. Chambers ◽

S. Delagrave ◽

J. Arroyo ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Yellow Fever ◽

Japanese Encephalitis ◽

Genetic Stability ◽

Vaccine Candidate ◽

Protective Efficacy ◽

Encephalitis Virus ◽

Live Attenuated Vaccine ◽

Attenuated Vaccine

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In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination.

The Journal of Cell Biology ◽

10.1083/jcb.111.3.1183 ◽

1990 ◽

Vol 111 (3) ◽

pp. 1183-1195 ◽

Cited By ~ 80

Author(s):

R Armstrong ◽

V L Friedrich ◽

K V Holmes ◽

M Dubois-Dalcq

Keyword(s):

Growth Factor ◽

Glial Cells ◽

Demyelinating Disease ◽

Hepatitis Virus ◽

Relative Proportion ◽

Biological Properties ◽

Murine Hepatitis Virus ◽

Adult Mice ◽

Igf I

A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease.

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