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Rescued influenza A virus with codon deoptimized NS1 gene is attenuated both in vitro and in vivo / 生物工程学报
Chinese Journal of Biotechnology ; (12): 720-726, 2009.
Artículo en Chino | WPRIM | ID: wpr-286651
ABSTRACT
Abstract To develop novel live attenuated influenza vaccine, we explored the feasibility to attenuate influenza virus by codon deoptimization of NS1. According to the codon usage bias in influenza A virus, we designed and synthesized a condon-deoptimized NS gene by substituting codons of 110 amino acids in the NS1 gene of A/Puerto Rico/8/34(H1N1) with unpreferred synonymous codons. The influenza A virus with the codon deoptimized NS1 gene (deoNS virus) was rescued by reverse genetics. Plaque forming assay and virus growth curve showed that the growth of deoNS virus was reduced about 1000 times in MDCK cells compared to that of the wild-type virus. Intranasal inoculation with deoNS virus did not cause death or evident disease in infected BALB/c mice. Furthermore, the virus titer in the lungs of mice infected with deoNS virus was significantly lower (i.e. 100-1000 times) than that of wild-type virus. Our results indicated that influenza virus could be effectively attenuated by synonymous codon deoptimization of NS1 gene. This strategy will be useful to develop new attenuated candidates for the production of live attenuated influenza vaccines.
Asunto(s)
Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Virus de la Influenza A / Recombinación Genética / Virulencia / Codón / Datos de Secuencia Molecular / Vacunas contra la Influenza / Vacunas Atenuadas / Secuencia de Bases / Proteínas no Estructurales Virales / Infecciones por Orthomyxoviridae Límite: Animales Idioma: Chino Revista: Chinese Journal of Biotechnology Año: 2009 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Virus de la Influenza A / Recombinación Genética / Virulencia / Codón / Datos de Secuencia Molecular / Vacunas contra la Influenza / Vacunas Atenuadas / Secuencia de Bases / Proteínas no Estructurales Virales / Infecciones por Orthomyxoviridae Límite: Animales Idioma: Chino Revista: Chinese Journal of Biotechnology Año: 2009 Tipo del documento: Artículo