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Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells

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 aff...

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Autores principales: Ye, Qian, Phan, Thu, Hu, Wei-Shou, Liu, Xuping, Fan, Li, Tan, Wen-Song, Zhao, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620111/
https://www.ncbi.nlm.nih.gov/pubmed/34835006
http://dx.doi.org/10.3390/v13112200
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author Ye, Qian
Phan, Thu
Hu, Wei-Shou
Liu, Xuping
Fan, Li
Tan, Wen-Song
Zhao, Liang
author_facet Ye, Qian
Phan, Thu
Hu, Wei-Shou
Liu, Xuping
Fan, Li
Tan, Wen-Song
Zhao, Liang
author_sort Ye, Qian
collection PubMed
description 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.
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spelling pubmed-86201112021-11-27 Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells Ye, Qian Phan, Thu Hu, Wei-Shou Liu, Xuping Fan, Li Tan, Wen-Song Zhao, Liang Viruses Article 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. MDPI 2021-11-01 /pmc/articles/PMC8620111/ /pubmed/34835006 http://dx.doi.org/10.3390/v13112200 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ye, Qian
Phan, Thu
Hu, Wei-Shou
Liu, Xuping
Fan, Li
Tan, Wen-Song
Zhao, Liang
Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells
title Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells
title_full Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells
title_fullStr Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells
title_full_unstemmed Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells
title_short Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells
title_sort transcriptomic characterization reveals attributes of high influenza virus productivity in mdck cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620111/
https://www.ncbi.nlm.nih.gov/pubmed/34835006
http://dx.doi.org/10.3390/v13112200
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