Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 10; p. 2322
• Main Authors: Lin, Ching-Hung, Yang, Cheng-Yao, Wang, Meilin, Ou, Shan-Chia, Lo, Chen-Yu, Tsai, Tsung-Lin, Wu, Hung-Yi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.10.2020; MDPI
• Subjects: Adaptation; Animals; Betacoronavirus - genetics; Cattle; Cell Line; Computational Biology; coronavirus; Coronavirus Infections - pathology; Coronavirus Infections - virology; Coronavirus, Bovine - genetics; Coronaviruses; Disease control; DNA polymerase; Gene expression; Gene Expression Regulation, Viral - genetics; Genetic aspects; genome structure; Genome, Viral - genetics; Genomes; Health aspects; Humans; Infections; Medical research; Microbiological research; Mutation; Pathogenicity; persistence; Persistent infection; Physiological adaptation; Physiological aspects; Proteins; Regulatory sequences; Regulatory Sequences, Ribonucleic Acid - genetics; RNA, Messenger - genetics; RNA, Viral - genetics; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Transcription; Transcription, Genetic - genetics; virus fitness; Viruses; Taiwan; United States > US; pathogenicity; coronavirus; persistence; virus fitness; genome structure; gene expression
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9102322

Coronaviruses are able to establish persistence. However, how coronaviruses react to persistence and whether the selected viruses have altered their characteristics remain unclear. In this study, we found that the persistent infection of bovine coronavirus (BCoV), which is in the same genus as SARS-COV-2, led to alterations of genome structure, attenuation of gene expression, and the synthesis of subgenomic mRNA (sgmRNA) with a previously unidentified pattern. Subsequent analyses revealed that the altered genome structures were associated with the attenuation of gene expression. In addition, the genome structure at the 5′ terminus and the cellular environment during the persistence were responsible for the sgmRNA synthesis, solving the previously unanswered question regarding the selection of transcription regulatory sequence for synthesis of BCoV sgmRNA 12.7. Although the BCoV variants (BCoV-p95) selected under the persistence replicated efficiently in cells without persistent infection, its pathogenicity was still lower than that of wild-type (wt) BCoV. Furthermore, in comparison with wt BCoV, the variant BCoV-p95 was not able to efficiently adapt to the challenges of alternative environments, suggesting wt BCoV is genetically robust. We anticipate that the findings derived from this fundamental research can contribute to the disease control and treatments against coronavirus infection including SARS-CoV-2.