Figure 7.

Model of VEEV infection induced transcriptional dysregulation leading to cell cycle delay. Upon VEEV infection, capsid blocks nucleocytoplasmic trafficking through forming a tetrameric complex with CRM1, importin α and importin β. This block results in transcriptional suppression, including an overall decrease in cell cycling associated transcripts, inducing a delay primarily at G₀/G₁. Nucleocytoplasmic trafficking is intact in uninfected cells. Proteins affected by the block in nucleocytoplasmic trafficking were not determined in this study but are hypothesized to be transcription factors, cell cycle regulators and/or mitotic assembly factors. The specific cyclin and cdk proteins affected following VEEV infection are indicated. Bolded cyclins (cyclin E and A) were decreased at both the mRNA and protein level, whereas expression of the unbolded cyclins and cdks were only assessed at the mRNA level. ^*Cyclin D mRNA expression was not altered but protein levels were decreased.