Roles of regulated intramembrane proteolysis in virus infection and antiviral immunity

• Regulated intramembrane proteolysis (RIP) is a signaling mechanism for host cells to orchestrate antiviral responses.
• Intramembrane proteases involved in RIP can be hijacked by virus to facilitate progression of the viral life cycle.
• Understanding the roles of RIP in host–virus interactions may reveal novel strategies to combat viral infection.

Regulated intramembrane proteolysis (RIP) is a signaling mechanism through which transmembrane precursor proteins are cleaved to liberate their cytoplasmic and/or luminal/extracellular fragments from membranes so that these fragments are able to function at a new location. Recent studies have indicated that this proteolytic reaction plays an important role in host–virus interaction. On one hand, RIP transfers the signal from the endoplasmic reticulum (ER) to nucleus to activate antiviral genes in response to alteration of the ER caused by viral infection. On the other hand, RIP can be hijacked by virus to process transmembrane viral protein precursors and to destroy transmembrane antiviral proteins. Understanding this Yin and Yang side of RIP may lead to new strategies to combat viral infection. This article is part of a Special Issue entitled: Intramembrane Proteases.

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