Virus Expression Database

GSE18791

Antiviral response dictated by choreographed cascade of transcription factors

Submitted by Uri Hershberg (Yale School of Medicine, USA) on Oct 28 2009

Platform: microarray – [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

Pubmed: 20164420

Summary The dendritic cell (DC) is a master regulator of immune responses. Pathogenic viruses subvert normal immune function in DCs through the expression of immune antagonists. Understanding how these antagonists interact with the host immune system requires knowledge of the underlying genetic regulatory network that operates during an uninhibited antiviral response. In order to isolate and identify this network, we studied DCs infected with Newcastle Disease Virus (NDV), which is able to stimulate innate immunity and DC maturation through activation of RIG-I signaling, but lacks the ability to evade the human interferon response. To analyze this experimental model, we developed a new approach integrating genome-wide expression kinetics and time-dependent promoter analysis. We found that the genetic program underlying the antiviral cell state transition during the first 18-hours post-infection could be explained by a single regulatory network. Gene expression changes were driven by a step-wise multi-factor cascading control mechanism, where the specific transcription factors controlling expression changed over time. Within this network, most individual genes are regulated by multiple factors, indicating robustness against virus-encoded immune evasion genes. In addition to effectively recapitulating current biological knowledge, we predicted, and validated experimentally, antiviral roles for several novel transcription factors. More generally, our results show how a genetic program can be temporally controlled through a single regulatory network to achieve the large-scale genetic reprogramming characteristic of cell state transitions.

57 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM466183 2.1.AF.0 dendritic cell  control Uninfected
GSM466184 2.1.AF.6 dendritic cell  6 hrs control Uninfected
GSM466185 2.1.AF.10 dendritic cell  10 hrs control Uninfected
GSM466186 2.1.NDV.1 dendritic cell  1 hr NDV Avian orthoavulavirus 1
GSM466187 2.1.NDV.2 dendritic cell  2 hrs NDV Avian orthoavulavirus 1
GSM466188 2.1.NDV.4 dendritic cell  4 hrs NDV Avian orthoavulavirus 1
GSM466189 2.1.NDV.6 dendritic cell  6 hrs NDV Avian orthoavulavirus 1
GSM466190 2.1.NDV.8 dendritic cell  8 hrs NDV Avian orthoavulavirus 1
GSM466191 2.1.NDV.10 dendritic cell  10 hrs NDV Avian orthoavulavirus 1
GSM466192 2.1.NDV.12 dendritic cell  12 hrs NDV Avian orthoavulavirus 1
GSM466193 2.1.NDV.14 dendritic cell  14 hrs NDV Avian orthoavulavirus 1
GSM466194 2.1.NDV.16 dendritic cell  16 hrs NDV Avian orthoavulavirus 1
GSM466195 2.2.AF.0 dendritic cell  control Uninfected
GSM466196 2.2.AF.1 dendritic cell  1 hr control Uninfected
GSM466197 2.2.AF.2 dendritic cell  2 hrs control Uninfected
GSM466198 2.2.AF.6 dendritic cell  6 hrs control Uninfected
GSM466199 2.2.AF.10 dendritic cell  10 hrs control Uninfected
GSM466200 2.2.AF.18 dendritic cell  18 hrs control Uninfected
GSM466201 2.2.NDV.1 dendritic cell  1 hr NDV Avian orthoavulavirus 1
GSM466202 2.2.NDV.2 dendritic cell  2 hrs NDV Avian orthoavulavirus 1
GSM466203 2.2.NDV.4 dendritic cell  4 hrs NDV Avian orthoavulavirus 1
GSM466204 2.2.NDV.6 dendritic cell  6 hrs NDV Avian orthoavulavirus 1
GSM466205 2.2.NDV.8 dendritic cell  8 hrs NDV Avian orthoavulavirus 1
GSM466206 2.2.NDV.10 dendritic cell  10 hrs NDV Avian orthoavulavirus 1
GSM466207 2.2.NDV.12 dendritic cell  12 hrs NDV Avian orthoavulavirus 1
GSM466208 2.2.NDV.14 dendritic cell  14 hrs NDV Avian orthoavulavirus 1
GSM466209 2.2.NDV.16 dendritic cell  16 hrs NDV Avian orthoavulavirus 1
GSM466210 2.2.NDV.18 dendritic cell  18 hrs NDV Avian orthoavulavirus 1
GSM466211 3.1.AF.0 dendritic cell  control Uninfected
GSM466212 3.1.AF.1 dendritic cell  1 hr control Uninfected
GSM466213 3.1.AF.2 dendritic cell  2 hrs control Uninfected
GSM466214 3.1.AF.6 dendritic cell  6 hrs control Uninfected
GSM466215 3.1.AF.10 dendritic cell  10 hrs control Uninfected
GSM466216 3.1.AF.18 dendritic cell  18 hrs control Uninfected
GSM466217 3.1.NDV.1 dendritic cell  1 hr NDV Avian orthoavulavirus 1
GSM466218 3.1.NDV.2 dendritic cell  2 hrs NDV Avian orthoavulavirus 1
GSM466219 3.1.NDV.4 dendritic cell  4 hrs NDV Avian orthoavulavirus 1
GSM466220 3.1.NDV.6 dendritic cell  6 hrs NDV Avian orthoavulavirus 1
GSM466221 3.1.NDV.8 dendritic cell  8 hrs NDV Avian orthoavulavirus 1
GSM466222 3.1.NDV.10 dendritic cell  10 hrs NDV Avian orthoavulavirus 1
GSM466223 3.1.NDV.12 dendritic cell  12 hrs NDV Avian orthoavulavirus 1
GSM466224 3.1.NDV.14 dendritic cell  14 hrs NDV Avian orthoavulavirus 1
GSM466225 3.1.NDV.16 dendritic cell  16 hrs NDV Avian orthoavulavirus 1
GSM466226 3.1.NDV.18 dendritic cell  18 hrs NDV Avian orthoavulavirus 1
GSM466227 3.2.AF.0 dendritic cell  control Uninfected
GSM466228 3.2.AF.6 dendritic cell  6 hrs control Uninfected
GSM466229 3.2.AF.10 dendritic cell  10 hrs control Uninfected
GSM466230 3.2.NDV.1 dendritic cell  1 hr NDV Avian orthoavulavirus 1
GSM466231 3.2.NDV.2 dendritic cell  2 hrs NDV Avian orthoavulavirus 1
GSM466232 3.2.NDV.4 dendritic cell  4 hrs NDV Avian orthoavulavirus 1
GSM466233 3.2.NDV.6 dendritic cell  6 hrs NDV Avian orthoavulavirus 1
GSM466234 3.2.NDV.8 dendritic cell  8 hrs NDV Avian orthoavulavirus 1
GSM466235 3.2.NDV.10 dendritic cell  10 hrs NDV Avian orthoavulavirus 1
GSM466236 3.2.NDV.12 dendritic cell  12 hrs NDV Avian orthoavulavirus 1
GSM466237 3.2.NDV.14 dendritic cell  14 hrs NDV Avian orthoavulavirus 1
GSM466238 3.2.NDV.16 dendritic cell  16 hrs NDV Avian orthoavulavirus 1
GSM466239 3.2.NDV.18 dendritic cell  18 hrs NDV Avian orthoavulavirus 1