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MINI REVIEW article

Front. Cell. Infect. Microbiol.

Sec. Veterinary and Zoonotic Infection

This article is part of the Research TopicPerspectives in Veterinary and Zoonotic Infection: 2025View all 6 articles

Cell line bias in virus research: implications for viral propagation and biological interpretation

Provisionally accepted
  • 1National Centre for Foreign Animal Disease, Canadian Food Inspection Agency (CFIA), Winnipeg, Canada
  • 2University of Manitoba Department of Medical Microbiology and Infectious Diseases, Winnipeg, Canada

The final, formatted version of the article will be published soon.

Cell lines are essential tools in virology for propagating viruses for characterization studies. However, reliance on a few historically popular lines—such as Vero, BHK-21, and MDCK—can introduce bias and obscure important aspects of viral biology, such as entry mechanisms and replication dynamics. A review of over 6,000 publications revealed that a small number of cell lines are used disproportionately, often due to historical precedence and general permissiveness for viral infection. Gene expression analysis showed that while these lines are enriched for pro-viral process genes, many underutilized cell lines from diverse tissue types also exhibit similar profiles. This review calls for a more strategic, molecularly informed approach to cell line selection, including the development of molecular databases for non-human cell lines, identification of virologically relevant traits, and broader use of biologically diverse panels. Such a data-driven strategy is especially vital for studying emerging and zoonotic viruses, where accurate modeling of host–virus interactions is important. Expanding and refining cell line use will improve reproducibility and yield more accurate insights into viral pathogenesis.

Keywords: cell lines, Virus amplification, Virus propagation, Virus characterization, cell line expression

Received: 28 Jul 2025; Accepted: 28 Nov 2025.

Copyright: © 2025 Kim and Pickering. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ji-Young Kim

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