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\begin{document}

\title{Transcriptomic Characterization Reveals Attributes of High Influenza
Virus Productivity in MDCK Cells}



\author[1]{Qian Ye}%
\author[2]{Thu Phan}%
\author[3]{Wei-Shou Hu}%
\author[4]{Xuping Liu}%
\author[4]{Li Fan}%
\author[1]{Wen-Song Tan}%
\author[1]{Liang Zhao}%
\affil[1]{East China University of Science and Technology}%
\affil[2]{University of Minnesota Twin Cities}%
\affil[3]{University of Minnesota}%
\affil[4]{Shanghai BioEngine Sci-Tech Co., LTD}%


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  \date{May 26, 2024}


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\begin{abstract}
Madin-Darby Canine Kidney (MDCK) cell line is among the commonly used
cell lines for the production of influenza virus vaccine. As cell
culture-based manufacturing poses to replace egg-based process,
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. 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 to infection similarly, 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 response.
Taken together we postulate that high productivity of IAV hinges on the
balance between suppression of host functions to divert cellular
resources and sustain sufficient activities for virus replication. The
mechanistic insights on virus productivity can facilitate the process
optimization and cell line engineering for advancing influenza vaccine
manufacturing.%
\end{abstract}%



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