The Importance of Physiologically Relevant Cell Lines for Studying Virus-Host Interactions.
Viruses interact intimately with the host cell at nearly every stage of replication, and the cell model that is chosen to study virus infection is critically important. Although primary cells reflect the phenotype of healthy cells in vivo better than cell lines, their limited lifespan makes experimental manipulation challenging. However, many tumor-derived and artificially immortalized cell lines have defects in induction of interferon-stimulated genes and other antiviral defenses. These defects can affect virus replication, especially when cells are infected at lower, more physiologically relevant, multiplicities of infection. Understanding the selective pressures and mechanisms underlying the loss of innate signaling pathways is helpful to choose immortalized cell lines without impaired antiviral defense. We describe the trials and tribulations we encountered while searching for an immortalized cell line with intact innate signaling, and how directed immortalization of primary cells avoids many of the pitfalls of spontaneous immortalization.
Pathology and Molecular Medicine, McMaster University, 1280 Main Str. West, Hamilton, ON L8S 4L8, Canada. haredn@mcmaster.ca.
David
D
Hare
Pathology and Molecular Medicine, McMaster University, 1280 Main Str. West, Hamilton, ON L8S 4L8, Canada. susan_collins@hotmail.com.
Susan
S
Collins
Pathology and Molecular Medicine, McMaster University, 1280 Main Str. West, Hamilton, ON L8S 4L8, Canada. cuddinbp@mcmaster.ca.
Breanne
B
Cuddington
Pathology and Molecular Medicine, McMaster University, 1280 Main Str. West, Hamilton, ON L8S 4L8, Canada. mossk@mcmaster.ca.|Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Str. West, Hamilton, ON L8S 4L8, Canada. mossk@mcmaster.ca.
Karen
K
Mossman
D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D014780:Viruses / Q000276:immunology* / Q000472:pathogenicity*
antiviral defense; immortalized cell; interferon; interferon regulatory factor 3; interferon-stimulated genes; primary cell; signal transduction