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:	Qian Ye, Thu Phan, Wei-Shou Hu, Xuping Liu, Li Fan, Wen-Song Tan, Liang Zhao
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	influenza virus MDCK cells transcriptome host shutoff anti-viral responses Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b15f7dc0ab99456f88665db0217b1cdf
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spelling	oai:doaj.org-article:b15f7dc0ab99456f88665db0217b1cdf2021-11-25T19:13:16ZTranscriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells10.3390/v131122001999-4915https://doaj.org/article/b15f7dc0ab99456f88665db0217b1cdf2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2200https://doaj.org/toc/1999-4915The 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.Qian YeThu PhanWei-Shou HuXuping LiuLi FanWen-Song TanLiang ZhaoMDPI AGarticleinfluenza virusMDCK cellstranscriptomehost shutoffanti-viral responsesMicrobiologyQR1-502ENViruses, Vol 13, Iss 2200, p 2200 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	influenza virus MDCK cells transcriptome host shutoff anti-viral responses Microbiology QR1-502
spellingShingle	influenza virus MDCK cells transcriptome host shutoff anti-viral responses Microbiology QR1-502 Qian Ye Thu Phan Wei-Shou Hu Xuping Liu Li Fan Wen-Song Tan Liang Zhao Transcriptomic Characterization Reveals Attributes of High Influenza Virus Productivity in MDCK Cells
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.
format	article
author	Qian Ye Thu Phan Wei-Shou Hu Xuping Liu Li Fan Wen-Song Tan Liang Zhao
author_facet	Qian Ye Thu Phan Wei-Shou Hu Xuping Liu Li Fan Wen-Song Tan Liang Zhao
author_sort	Qian Ye
title	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_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_sort	transcriptomic characterization reveals attributes of high influenza virus productivity in mdck cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b15f7dc0ab99456f88665db0217b1cdf
work_keys_str_mv	AT qianye transcriptomiccharacterizationrevealsattributesofhighinfluenzavirusproductivityinmdckcells AT thuphan transcriptomiccharacterizationrevealsattributesofhighinfluenzavirusproductivityinmdckcells AT weishouhu transcriptomiccharacterizationrevealsattributesofhighinfluenzavirusproductivityinmdckcells AT xupingliu transcriptomiccharacterizationrevealsattributesofhighinfluenzavirusproductivityinmdckcells AT lifan transcriptomiccharacterizationrevealsattributesofhighinfluenzavirusproductivityinmdckcells AT wensongtan transcriptomiccharacterizationrevealsattributesofhighinfluenzavirusproductivityinmdckcells AT liangzhao transcriptomiccharacterizationrevealsattributesofhighinfluenzavirusproductivityinmdckcells
_version_	1718410176652902400

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

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