Back to Search
Start Over
Incompatible Translation Drives a Convergent Evolution and Viral Attenuation During the Development of Live Attenuated Vaccine.
- Source :
-
Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2018 Jul 18; Vol. 8, pp. 249. Date of Electronic Publication: 2018 Jul 18 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Live attenuated vaccines are widely used to protect humans or animals from pathogen infections. We have previously developed a chicken embryo-attenuated Duck Hepatitis A Virus genotype 1 (DHAV-1) vaccine (CH60 strain). This study aims to understand the mechanisms that drive a virulent strain to an attenuated virus. Here, we systematically compared five DHAV-1 chicken embryo attenuated strains and 68 virulent strains. Phylogenetic analysis indicated that duck virulent strains isolated from different geographic regions of China undergo a convergent evolution in the chicken embryos. Comparative analysis indicated that the codon usage bias of the attenuated strains were shaped by chicken codons usage bias, which essentially contributed to viral adaption in the unsuitable host driven by incompatible translation. Of note, the missense mutations in coding region and mutations in untranslated regions may also contribute to viral attenuation of DHAV-1 to some extent. Importantly, we have experimentally confirmed that the expression levels of four viral proteins ( 2A 3 pro , 2A 3 pro , 3C <superscript>pro</superscript> , and 3D <superscript>pro</superscript> ) in the liver and kidney of ducks infected with an attenuated strain are significantly lower than that infected with a virulent strain, despite with similar virus load. Thus, the key mechanisms of viral attenuation revealed by this study may lead to innovative and easy approaches in designing live attenuated vaccines.
- Subjects :
- Animals
Chick Embryo
China
Genotype
Kidney pathology
Kidney virology
Liver pathology
Liver virology
Mutation, Missense
Phylogeny
Sequence Analysis, DNA
Vaccines, Attenuated administration & dosage
Vaccines, Attenuated adverse effects
Vaccines, Attenuated genetics
Vaccines, Attenuated isolation & purification
Viral Hepatitis Vaccines adverse effects
Viral Hepatitis Vaccines genetics
Virulence
Directed Molecular Evolution
Hepatitis Virus, Duck growth & development
Hepatitis Virus, Duck pathogenicity
Protein Biosynthesis
Viral Hepatitis Vaccines administration & dosage
Viral Hepatitis Vaccines isolation & purification
Subjects
Details
- Language :
- English
- ISSN :
- 2235-2988
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Frontiers in cellular and infection microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 30073153
- Full Text :
- https://doi.org/10.3389/fcimb.2018.00249