Construction of a high-yield dengue virus by replacing nonstructural proteins 3-4B without increasing virulence
| Autor: | Magot Diata Omokoko, Kazuyoshi Ikuta, Sabar Pambudi, Supranee Phanthanawiboon, Wataru Kamitani, Keiko Hanabara, Takeshi Kurosu, Atchareeya A-nuegoonpipat |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
viruses Biophysics Virulence Dengue virus Biology Viral Nonstructural Proteins medicine.disease_cause Biochemistry Virus Dengue fever 03 medical and health sciences medicine Molecular Biology Recombination Genetic NS3 Attenuated vaccine virus diseases Cell Biology biochemical phenomena metabolism and nutrition Dengue Virus Viral Load medicine.disease Virology Vaccination 030104 developmental biology Genetic Enhancement Viral replication Batch Cell Culture Techniques |
| Zdroj: | Biochemical and biophysical research communications. 495(1) |
| ISSN: | 1090-2104 |
| Popis: | Producing virus at high yield is critically important for development of whole virion inactivated vaccines or live attenuated vaccines. Most dengue virus (DENV) clinical isolates, however, replicate at low levels in cultured cells, which limits their use for vaccine development. The present study examined differences between low-replicating DENV clinical isolates and high-replicating laboratory strains with the aim of engineering high-yield DENV clinical isolates. Construction of a series of recombinant chimeric viruses derived from a high-replicating laboratory DENV type 4 (DENV-4) H241 strain and a clinical isolate revealed that the NS3-NS4B region of H241 conferred a replication advantage in cultured cells. Furthermore, northern blot analysis revealed that this advantage was due to more efficient synthesis of viral RNA. Importantly, replacement of the NS3-NS4B region of H241 did not increase virulence in mice, suggesting that viral production can be increased safely. This study provided information that will facilitate engineering of safe and high-yield viruses that can be used for vaccine development. |
| Databáze: | OpenAIRE |
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