Characterization of poxvirus-encoded proteins that regulate innate immune signaling pathways.
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.
Division of Infectious Disease, Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA, USA.
Florentina
F
Rus
Kayla
K
Morlock
Neal
N
Silverman
Ngoc
N
Pham
Girish J
GJ
Kotwal
William L
WL
Marshall
D000595:Amino Acid Sequence; D017209:Apoptosis; D003001:Cloning, Molecular; D005434:Flow Cytometry; D017930:Genes, Reporter; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D056747:Immunomodulation; D047468:Immunoprecipitation; D049409:Luciferases, Firefly; D049410:Luciferases, Renilla; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D051193:Toll-Like Receptors; D014764:Viral Proteins; D049410:Luciferases, Renilla; D049409:Luciferases, Firefly