Frontiers in Cellular and Infection Microbiology (Jul 2018)
Incompatible Translation Drives a Convergent Evolution and Viral Attenuation During the Development of Live Attenuated Vaccine
- Xumin Ou,
- Xumin Ou,
- Xumin Ou,
- Mingshu Wang,
- Mingshu Wang,
- Mingshu Wang,
- Sai Mao,
- Sai Mao,
- Jingyu Cao,
- Jingyu Cao,
- Anchun Cheng,
- Anchun Cheng,
- Anchun Cheng,
- Dekang Zhu,
- Dekang Zhu,
- Shun Chen,
- Shun Chen,
- Shun Chen,
- Renyong Jia,
- Renyong Jia,
- Renyong Jia,
- Mafeng Liu,
- Mafeng Liu,
- Mafeng Liu,
- Qiao Yang,
- Qiao Yang,
- Qiao Yang,
- Ying Wu,
- Ying Wu,
- Ying Wu,
- Xinxin Zhao,
- Xinxin Zhao,
- Xinxin Zhao,
- Shaqiu Zhang,
- Shaqiu Zhang,
- Shaqiu Zhang,
- Yunya Liu,
- Yunya Liu,
- Yunya Liu,
- Yanling Yu,
- Yanling Yu,
- Yanling Yu,
- Ling Zhang,
- Ling Zhang,
- Ling Zhang,
- Xiaoyue Chen,
- Xiaoyue Chen,
- Maikel P. Peppelenbosch,
- Qiuwei Pan
Affiliations
- Xumin Ou
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Xumin Ou
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Xumin Ou
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands
- Mingshu Wang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Mingshu Wang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Mingshu Wang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Sai Mao
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Sai Mao
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Jingyu Cao
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Jingyu Cao
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Anchun Cheng
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Anchun Cheng
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Anchun Cheng
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Dekang Zhu
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Dekang Zhu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Shun Chen
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Shun Chen
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Shun Chen
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Renyong Jia
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Renyong Jia
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Renyong Jia
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Mafeng Liu
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Mafeng Liu
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Mafeng Liu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Qiao Yang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Qiao Yang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Qiao Yang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Ying Wu
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Ying Wu
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Ying Wu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Xinxin Zhao
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Xinxin Zhao
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Xinxin Zhao
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Shaqiu Zhang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Shaqiu Zhang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Shaqiu Zhang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Yunya Liu
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Yunya Liu
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Yunya Liu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Yanling Yu
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Yanling Yu
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Yanling Yu
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Ling Zhang
- Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Ling Zhang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Ling Zhang
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Xiaoyue Chen
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu, China
- Xiaoyue Chen
- Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Maikel P. Peppelenbosch
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands
- Qiuwei Pan
- Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, Netherlands
- DOI
- https://doi.org/10.3389/fcimb.2018.00249
- Journal volume & issue
-
Vol. 8
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 (2A3pro, 2A3pro, 3Cpro, and 3Dpro) 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.
Keywords
