文献类型：期刊文献

英文题名：Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells

作者：Ye, Qian[1,2];Phan, Thu[2];Hu, Wei-Shou[2];Liu, Xuping[3];Fan, Li[3];Tan, Wen-Song[1,3];Zhao, Liang[1,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Univ Minnesota, Dept Chem Engn & Mat Sci, 421 Washington Ave SE, Minneapolis, MN 55455 USA;[3]Shanghai BioEngine Sci Tech Co Ltd, Res & Dev Ctr, Shanghai 201203, Peoples R China

年份：2021

卷号：13

期号：11

外文期刊名：VIRUSES-BASEL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000723908500001)】；

语种：英文

外文关键词：influenza virus; MDCK cells; transcriptome; host shutoff; anti-viral responses

摘要：The Madin-Darby Canine Kidney (MDCK) cell line is among the most commonly used cell lines for the production of influenza virus vaccines. As cell culture-based manufacturing is poised to replace egg-based processes, increasing virus production is of paramount importance. To shed light on factors affecting virus productivity, we isolated a subline, H1, which had twice the influenza virus A (IAV) productivity of the parent (P) through cell cloning, and characterized H1 and P in detail on both physical and molecular levels. Transcriptome analysis revealed that within a few hours after IAV infection, viral mRNAs constituted over one fifth of total mRNA, with several viral genes more highly expressed in H1 than P. Functional analysis of the transcriptome dynamics showed that H1 and P responded similarly to IAV infection, and were both subjected to host shutoff and inflammatory responses. Importantly, H1 was more active in translation and RNA processing intrinsically and after infection. Furthermore, H1 had more subdued inflammatory and antiviral responses. Taken together, we postulate that the high productivity of IAV hinges on the balance between suppression of host functions to divert cellular resources and the sustaining of sufficient activities for virus replication. Mechanistic insights into virus productivity can facilitate the process optimization and cell line engineering for advancing influenza vaccine manufacturing.