The role of the IKK complex in viral infections

Abstract

The NF-κB signal transduction pathway is a critical regulator of multiple cellular functions that ultimately shift the balance between cell survival and death. The cascade is activated by many intrinsic and extrinsic stimuli, which is transduced via adaptor proteins to phosphorylate the IκB kinase (IKK) complex, which in turn phosphorylates the inhibitory IκBα protein to undergo proteasomal degradation and sets in motion nuclear events in response to the initial stimulus. Viruses are important modulators of the NF-κB cascade and have evolved multiple mechanisms to activate or inhibit this pathway in a manner conducive to viral multiplication and establishment of a productive infectious cycle. This is a subject of extensive research by multiple laboratories whereby unraveling the interactions between specific viral components and members of the NF-κB signal transduction cascade can shed unique perspectives on infection associated pathogenesis and novel therapeutic targets. In this review, we highlight the interactions between components of the IKK complex and multiple RNA and DNA viruses with the emphasis on mechanisms by which the interaction feeds the infection. Understanding these interactions will shed light on the exploitative capabilities of viruses to maintain an environment favorable for a productive infection.

Keywords: IKK complex; host response; viral proteins.