Influenza passaging annotations: what they tell us and why we should listen

DuPai, Cory D.; McWhite, Claire D.; Smith, Catherine; Garten, Rebecca; Maurer‐Stroh, Sebastian; Wilke, Claus O.

doi:10.1093/ve/vez016

Cited by 10 publications

(13 citation statements)

References 34 publications

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“…in wild-type MDCK cells often have mutations around their Sia binding sites (32,55). We saw no significant difference in the SNVs near the HA receptor-binding sites of pH1N1 when passed in MDCK-WT or MDCK-SiaT1 cells.…”

Section: Mdck-siat1 Cells Have Higher Expression Of This Form Of Sia mentioning

confidence: 61%

Influenza A viruses serially passaged in different MDCK cell lines exhibit limited sequence variation across their genomes, with the exception of the hemagglutinin gene

Barnard

Wasik

Alford-Lawrence

et al. 2020

Preprint

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New methods for deep sequence analysis provide an opportunity to follow the emergence and dynamics of virus mutations in real time. Although viruses are commonly grown in cell culture 30 for research and for vaccine development, the cells used to grow the virus are often not derived from the same tissue or even the same host that the virus naturally replicates in. The selective pressures of culturing virus in vitro are still only partially understood. MDCK cells are the standard cell for growing influenza viruses yet are derived from the epithelium of the canine kidney and are also heterogenous. We passaged human H3N2, H1N1 pandemic, and canine However, the selection pressures that cell passaging imposes on viruses are often poorly 3 understood. We used deep sequence analysis to define, in detail, how three different influenza A viruses respond to passaging in different lineages of canine MDCK cells that are commonly used for their growth, as well as in variant cells engineered to express different forms of their cell surface receptor, sialic acid. This analysis revealed that most mutations occur in the HA 55 gene and few sequence changes in the virus population reached high proportions. This is relevant for understanding the selective pressures of virus growth in cell culture and how it shapes evolutionary patterns. 148 words

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Section: Mdck-siat1 Cells Have Higher Expression Of This Form Of Sia mentioning

confidence: 61%

Influenza A viruses serially passaged in different MDCK cell lines exhibit limited sequence variation across their genomes, with the exception of the hemagglutinin gene

Barnard

Wasik

Alford-Lawrence

et al. 2020

Preprint

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“…Passage annotation is available in GISAID’s EpiFlu database, the most complete source for influenza sequences, but annotation submission has historically been heterogeneous without controlled vocabulary [18]. For example, ‘M1’, ‘MDCK3’ or ‘MDCK 2 + 2’ all refer to passage in Madin-Darby Canine Kidney (MDCK) cells.…”

Section: Methodsmentioning

confidence: 99%

Influenza A Hemagglutinin Passage Bias Sites and Host Specificity Mutations

Lee

Chang

Russell

et al. 2019

Cells

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Animal studies aimed at understanding influenza virus mutations that change host specificity to adapt to replication in mammalian hosts are necessarily limited in sample numbers due to high cost and safety requirements. As a safe, higher-throughput alternative, we explore the possibility of using readily available passage bias data obtained mostly from seasonal H1 and H3 influenza strains that were differentially grown in mammalian (MDCK) and avian cells (eggs). Using a statistical approach over 80,000 influenza hemagglutinin sequences with passage information, we found that passage bias sites are most commonly found in three regions: (i) the globular head domain around the receptor binding site, (ii) the region that undergoes pH-dependent structural changes and (iii) the unstructured N-terminal region harbouring the signal peptide. Passage bias sites were consistent among different passage cell types as well as between influenza A subtypes. We also find epistatic interactions of site pairs supporting the notion of host-specific dependency of mutations on virus genomic background. The sites identified from our large-scale sequence analysis substantially overlap with known host adaptation sites in the WHO H5N1 genetic changes inventory suggesting information from passage bias can provide candidate sites for host specificity changes to aid in risk assessment for emerging strains.

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“…]. Although influenza virus evolution can be investigated in traditional influenza models (e.g., cell lines, chicken eggs, and animals), it has long been known that nonhuman models can introduce false adaption mutations, which has raised a major stumbling block to influenza research in the wider medical community [ 66. , 67.…”

Section: Modeling Viral Diseases In Organ Chipsmentioning

confidence: 99%

Human Organs-on-Chips for Virology

Tang

Abouleila

et al. 2020

Trends in Microbiology

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While conventional in vitro culture systems and animal models have been used to study the pathogenesis of viral infections and to facilitate development of vaccines and therapeutics for viral diseases, models that can accurately recapitulate human responses to infection are still lacking. Human organ-on-a-chip (Organ Chip) microfluidic culture devices that recapitulate tissue–tissue interfaces, fluid flows, mechanical cues, and organ-level physiology have been developed to narrow the gap between in vitro experimental models and human pathophysiology. Here, we describe how recent developments in Organ Chips have enabled re-creation of complex pathophysiological features of human viral infections in vitro .

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Influenza passaging annotations: what they tell us and why we should listen

Cited by 10 publications

References 34 publications

Influenza A viruses serially passaged in different MDCK cell lines exhibit limited sequence variation across their genomes, with the exception of the hemagglutinin gene

Influenza A viruses serially passaged in different MDCK cell lines exhibit limited sequence variation across their genomes, with the exception of the hemagglutinin gene

Influenza A Hemagglutinin Passage Bias Sites and Host Specificity Mutations

Human Organs-on-Chips for Virology

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