Suppression of proinflammatory signal transduction and gene expression by the dual nucleic acid binding domains of the vaccinia virus E3L proteins.
Cells have evolved elaborate mechanisms to counteract the onslaught of viral infections. To activate these defenses, the viral threat must be recognized. Danger signals, or pathogen-associated molecular patterns, that are induced by pathogens include double-stranded RNA (dsRNA), viral single-stranded RNA, glycolipids, and CpG DNA. Understanding the signal transduction pathways activated and host gene expression induced by these danger signals is vital to understanding virus-host interactions. The vaccinia virus E3L protein is involved in blocking the host antiviral response and increasing pathogenesis, functions that map to separate C-terminal dsRNA- and N-terminal Z-DNA-binding domains. Viruses containing mutations in these domains allow modeling of the role of dsRNA and Z-form nucleic acid in the host response to virus infection. Deletions in the Z-DNA- or dsRNA-binding domains led to activation of signal transduction cascades and up-regulation of host gene expression, with many genes involved in the inflammatory response. These data suggest that poxviruses actively inhibit cellular recognition of viral danger signals and the subsequent cellular response to the viral threat.
Langland
Jeffrey O
JO
School of Life Sciences, Faculty of Biomedicine and Biotechnology, Arizona State University, Tempe, AZ 85287-4501, USA.
Kash
John C
JC
Carter
Victoria
V
Thomas
Matthew J
MJ
Katze
Michael G
MG
Jacobs
Bertram L
BL
D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D015398:Signal Transduction; D014616:Vaccinia virus / Q000276:immunology* / Q000502:physiology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C081374:E3L protein, Vaccinia virus; D016601:RNA-Binding Proteins; D014764:Viral Proteins