Rotavirus Induction and Evasion of Innate Immunity
Innate immune responses by the host are the first line of defence against invading viruses. Viral components are recognised by host cells, triggering the production of type I interferon and other cytokines that can attract immune cells and boost the adaptive immune response. Interferon also signals surrounding cells to initiate an antiviral state, protecting them from infection. Our laboratory is interested in various aspects of innate immunity to rotavirus, including the mechanism of rotavirus recognition by host cells and how this leads to interferon and cytokine production. We also are determining how interferon inhibits rotavirus replication.
Figure 1: Inhibition of interferon signalling by rotavirus. Upon stimulation with interferon α, STAT2 (red) is prevented from entering the nucleus (blue) of rotavirus-infected cells (green).
Members of our laboratory also study the strategies used by rotavirus to evade innate immune responses. We have shown that rotavirus blocks interferon signalling by preventing the targeting of STAT transcription factors to the nucleus (Figure 1). This may help rotavirus replicate in cells that are exposed to interferon and are transitioning to an antiviral state. We have also shown that rotavirus inhibits signalling through the NFκB transcription factor, which may prevent the production of cytokines in infected cells and dampen the immune response to rotavirus infection.
The study of innate responses to rotavirus and how rotavirus counteracts these responses will improve our understanding of rotavirus disease and benefit vaccine design.
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