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Characterization of Poxvirus-Encoded Proteins that Regulate Innate Immune Signaling Pathways

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Vaccinia Virus and Poxvirology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 890))

Abstract

Innate immune recognition of pathogens is critical to the prompt control of infections, permitting the host to survive to develop long-term immunity via an adaptive immune response. Poxviruses encode a family of proteins that inhibit signaling by Toll-like receptors to their downstream signaling components, severely limiting nuclear translocation of transcription factors such as IRF3 and NF-κB and thereby decreasing production of host interferons and cytokines. We describe bioinformatics techniques for identifying candidate poxviral inhibitors of the innate immune response based on similarity to the family of proteins that includes A52, A46, and N1. Robust luciferase assays can determine whether a given poxviral gene affects innate immune signaling, and in combination with other approaches can identify the cellular targets of poxviral innate immune evasion genes. Because apoptosis is an innate immune response of the cell to viral infection, assays for identifying poxviral genes that inhibit apoptosis can also be employed. Novel poxviral innate immune inhibitors are being identified via several approaches and these techniques promise to identify further complexities in the way that poxviruses interact with the host innate immune system.

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Acknowledgments

We would like to acknowledge the invaluable advice of Eicke Latz, Kate Fitzgerald, Andrew Bowie, Brian Monks, and Doug Golenbock. This project has been funded in whole or part with funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health: R01 AI070940 to W.L.M. and R21AI069167 to N.S.

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Authors and Affiliations

  1. Division of Infectious Disease, Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA, USA

    Florentina Rus, Kayla Morlock, Neal Silverman, Ngoc Pham & William L. Marshall

  2. Kotwal Bioconsulting, LLC, Louisville, KY, USA

    Girish J. Kotwal

  3. InFlaMed Inc, Louisville, KY, USA

    Girish J. Kotwal

  4. Department of Microbiology and Biochemistry, University of Medicine and Health Sciences, Saint Kitts, West Indies

    Girish J. Kotwal

Authors
  1. Florentina Rus
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  2. Kayla Morlock
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  3. Neal Silverman
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  4. Ngoc Pham
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  5. Girish J. Kotwal
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  6. William L. Marshall
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Corresponding authors

Correspondence to Girish J. Kotwal or William L. Marshall .

Editor information

Editors and Affiliations

  1. School of Medicine and the Philadelphia, Division of Infectious Disease, University of Pennsylvania, Johnson Pavilion 502, Philadelphia, 19104-6073, Pennsylvania, USA

    Stuart N. Isaacs

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© 2012 Springer Science+Business Media, LLC

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Rus, F., Morlock, K., Silverman, N., Pham, N., Kotwal, G.J., Marshall, W.L. (2012). Characterization of Poxvirus-Encoded Proteins that Regulate Innate Immune Signaling Pathways. In: Isaacs, S. (eds) Vaccinia Virus and Poxvirology. Methods in Molecular Biology, vol 890. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-876-4_16

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  • DOI: https://doi.org/10.1007/978-1-61779-876-4_16

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-875-7

  • Online ISBN: 978-1-61779-876-4

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