Ching-Juh Lai, Ph.D.
Studies are focused on dengue viruses and other related insect-borne flaviviruses, such as Japanese encephalitis virus and tickborne encephalitis virus, with a goal to develop vaccines against these viruses. A range of molecular techniques has been used to characterize the functions of the viral structural and nonstructural proteins during viral replication and for display of virulence; to analyze the antigenic structure and design strategies to increase the immunogenicity of the major envelope-protective antigen in animal models; and to develop subunit as well as live virus approaches to vaccines against dengue and other flaviviruses.
Currently, scientists are using the dengue type 4 cDNA clone to create chimeric viruses containing genes from different dengue serotypes or from other flaviviruses and thus displaying the antigenicity of these viruses. We are also investigating the molecular mechanisms responsible for dengue virus attenuation in humans through analysis of mutations present in virus strains selected by serial passage in the mouse brain. Investigators have shown that these mouse-passaged virus strains exhibited significant attenuation for humans.
Similarly, full-length cDNA clones of Langat virus, a member of the tickborne encephalitis virus group, are employed to investigate immunogenicity and virulence in animal models. Mutants containing deletions that reduce the capacity of virus replication in cell culture or conditional mutants should also prove valuable for evaluation of the attenuation phenotype. Defined mutations are introduced into cDNA and transferred into infectious viral mutants, which may be used as candidate live vaccine strains.
Ruhe Men, Golam Shameem, Grigori Prikhodko, Tetsu Yamashiro.
(View current list in PubMed.)
Bray M, Men R, Lai CJ. Monkeys immunized with intertypic chimeric dengue viruses are protected against wild type virus challenge. J Virol. 1996. 70: 4162-4266.
Hiramatsu K, Tadano M, Men R, Lai CJ. Mutational analysis of a neutralization epitope on the dengue type 2 virus (DEN2) envelope protein: monoclonal antibody resistant DEN2/DEN4 chimeras exhibit reduced mouse neurovirulence. Virology. 1996. 224: 437-445.
Men R, Bray M, Clark D, Chanock R, Lai CJ. Dengue type 4 virus mutants containing deletions in the 3' noncoding region of the RNA genome: analysis of growth restriction in cell culture and altered viremia pattern and immunogenicity in rhesus monkeys. J Virol. 1996. 70: 3930-3937.
Pletnev AG, Men R. Attenuation of the Langat tick-borne flavivirus by chimerization with mosquito-borne flavivirus dengue type 4. Proc Nat Acad Sci USA. 1998. 95: 1746-1751.
Bray M, Men R, Tokimatsu I, Lai CJ. Genetic determinants responsible for acquisition of dengue type 2 virus mouse neurovirulence. J Virol. 1998. 72: 1647-1651.
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Last Updated May 21, 2006