ID: 108: Spatial insights in the interaction between the RIG-I like receptor pathway and viral proteins

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• 作者：Maria Teresa Sá ; nchez-Aparicio¹ ; ² ; Juan Ayllon¹ ; ² ; Adolfo Garcí ; a-Sastre¹ ; ² ; ³
• 刊名：Cytokine
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：76
• 期：1
• 页码：85
• 全文大小：41 K

文摘

The innate immune response relies on a set of Pathogen Recognition Receptors (PRRs) that sensor pathogen patterns (PAMPs). RIG-I is a cytosolic PRR that detects 5’-triphosphate double-stranded RNAs produced during infection. Once activated, the pathway leads to the induction of type I IFN and proinflammatory cytokines, leading to a cellular antiviral state. Upon recognition of the RNA, RIG-I hydrolyzes ATP and changes its conformation to an active state. The CARD domains are then exposed and become K63-linked polyubiquitinated by E3-ligases, such as TRIM25.

The activation of this pathway is complex and well characterized, but most of the spatio-temporal events, and the subcellular localization where the essential proteins interact, are still under interrogation. Through different techniques, we analyzed how these proteins form complexes that are distributed and reorganized spatially within the cell in order to create an efficient antiviral state.

RIG-I is the main sensor for recognition of viruses such as Paramyxoviruses, Flaviviruses, Rhabdoviruses and Orthomyxoviruses. Many of them have developed numerous and different strategies to overcome the activation of the RLR pathway. We will discuss and show new insights on how, where, and when, viral proteins can counteract the activation of the RLR pathway. NS1 of Influenza A virus, or NS3/4A of Hepatitis C Virus, as an example, are IFN antagonistic viral proteins that interact with specific complexes in very well defined areas in the host cell in order to inhibit the antiviral state in an infected cell.