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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/179355
Advances for the Hepatitis A virus antigen production using a virus strain with codon frequency optimization adjustments in specific locations
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The available cell-adapted hepatitis A virus (HAV) strains show a very slow replication phenotype hampering the affordable production of antigen. A fast-growing strain characterized by the occurrence of mutations in the internal ribosome entry site (IRES), combined with changes in the codon composition has been selected in our laboratory. A characterization of the IRES activity of this fast-growing strain (HM175-HP; HP) vs. its parental strain (HM175; L0) was assessed in two cell substrates used in vaccine production (MRC-5 and Vero cells) compared with the FRhK-4 cell line in which its selection was performed. The HP-derived IRES was significantly more active than the L0-derived IRES in all cells tested and both IRES were more active in the FRhK-4 cells. The translation efficiency of the HP-derived IRES was also much higher than the L0-derived IRES, particularly, in genes with a HP codon usage background. These results correlated with a higher virus production in a shorter time for the HP strain compared to the L0 strain in any of the three cell lines tested, and of both strains in the FRhK-4 cells compared to Vero and MRC-5 cells. The addition of wortmannin resulted in the increase of infectious viruses and antigen in the supernatant of FRhK-4 infected cells, independently of the strain. Finally, the replication of both strains in a clone of FRhK-4 cells adapted to grow with synthetic sera was optimal and again the HP strain showed higher yields.
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CHAVARRIA MIRÓ, Gemma, CASTELLARNAU SERRA, Montserrat de, FUENTES, Cristina, D'ANDREA RODRÍGUEZ-VIDA, Lucía, PÉREZ-RODRÍGUEZ, Francisco javier, BEGUIRISTAIN, Nerea, BOSCH, Albert, GUIX ARNAU, Susana, PINTÓ SOLÉ, Rosa maría. Advances for the Hepatitis A virus antigen production using a virus strain with codon frequency optimization adjustments in specific locations. _Frontiers in Microbiology_. 2021. Vol. 12, núm. 255. [consulta: 26 de febrer de 2026]. ISSN: 1664-302X. [Disponible a: https://hdl.handle.net/2445/179355]