Ubiquitin and SUMO in Antiviral Defence
Van G. Wilson
from: SUMOylation and Ubiquitination: Current and Emerging Concepts (Edited by: Van G. Wilson). Caister Academic Press, U.K. (2019) Pages: 389-416.
Abstract
The three branches of immunity, intrinsic, innate, and acquired, are each critical for antiviral defense. Intrinsic immunity consists of immediate, pre-existing mechanisms to limit replication and spread of invading viruses. Innate immunity produces a massive response to generate secreted interferons and cytokines that generate an antiviral state in recipient cells that can reduce viral reproduction through multiples mechanisms. Additionally, these secreted chemokines help prime the acquired immune response. The acquired immune response has two arms, the cellular and the humoral. Collectively these responses will finally clear infections and establish long-lasting protection through immune memory. Each of these complex systems needs careful regulation to ensure timely and faithful response to foreign pathogens and to ensure that the responses are down-regulated appropriately to prevent excessive host cell damage. Major regulators of immunity include ubiquitin and ubiquitin-like (Ubls) proteins, primarily the SUMO family. Ubiquitin and SUMOs are post-translationally attached to many immune system proteins to either activate or reduce target protein function. These modifications are in turn reversible via specific proteases (deubiquitinases or SUMO proteases known as SENPs) adding further dynamic regulation through varying the levels of modification and demodification. Additionally, there are several examples where free chains of polyubiquitin provide activating function by acting as a scaffold to recruit individual proteins into a functional, multiprotein complex. This chapter will explore specific examples of how each branch of the immune system is critically dependent on ubiquitin and/or Ubls for normal response to viral pathogens read more ...
