Author:
Lin Ching-Hung,Hsieh Feng-Cheng,Lai Chien-Chen,Wang Wei-Chen,Kuo Cheng-Yu,Yang Chun-Chun,Hsu Hsuan-Wei,Tam Hon-Man-Herman,Yang Cheng-Yao,Wu Hung-Yi
Abstract
AbstractDuring coronavirus infection, in addition to the well-known coronavirus genomes and subgenomic mRNAs, an abundance of defective viral genomes (DVGs) can also be synthesized. In this study, we aimed to examine whether DVGs can encode proteins in infected cells. Nanopore direct RNA sequencing and liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis were employed. With the protein databases generated by nanopore direct RNA sequencing and the cell lysates derived from the RNA–protein pull-down assay, six DVG-encoded proteins were identified by LC–MS/MS based on the featured fusion peptides caused by recombination during DVG synthesis. The results suggest that the coronavirus DVGs have the capability to encode proteins. Consequently, future studies determining the biological function of DVG-encoded proteins may contribute to the understanding of their roles in coronavirus pathogenesis and the development of antiviral strategies.
Funder
National Science and Technology Council
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Virology
Reference35 articles.
1. Brian DA, Baric RS. Coronavirus genome structure and replication. Curr Top Microbiol Immunol. 2005;287:1–30.
2. Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res. 2006;117(1):17–37.
3. Xiao SY, Wu YJ, Liu H. Evolving status of the 2019 novel coronavirus infection: proposal of conventional serologic assays for disease diagnosis and infection monitoring. J Med Virol. 2020;92(5):464–7.
4. Yang WJ, Cao QQ, Qin L, Wang XY, Cheng ZH, Pan AS, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China. J Infect. 2020;80(4):388–93.
5. Sawicki SG, Sawicki DL. Coronavirus transcription: a perspective. Curr Top Microbiol Immunol. 2005;287:31–55.