Mitochondrial antiviral-signaling protein

Mitochondrial antiviral-signaling protein (MAVS), also known as IPS-1, VISA, and Cardif, is a key protein involved in the innate immune response to viral infections. MAVS is encoded by the MAVS gene in humans and plays a crucial role in the immune system by mediating antiviral signaling pathways.

Structure

MAVS is a mitochondrial membrane protein that contains an N-terminal caspase recruitment domain (CARD), a proline-rich region, and a C-terminal transmembrane domain. The CARD domain is essential for the interaction with other CARD-containing proteins, such as RIG-I and MDA5, which are cytoplasmic sensors of viral RNA.

Function

MAVS is pivotal in the activation of the type I interferon response. Upon recognition of viral RNA by RIG-I or MDA5, these sensors undergo conformational changes and interact with MAVS through CARD-CARD interactions. This interaction leads to the formation of a signaling complex on the mitochondrial membrane, which subsequently activates downstream signaling pathways, including the NF-κB and IRF3 pathways. The activation of these pathways results in the production of type I interferons and other pro-inflammatory cytokines, which are essential for the antiviral response.

Role in Disease

Mutations or dysregulation of MAVS can lead to impaired antiviral responses and increased susceptibility to viral infections. Additionally, some viruses have evolved mechanisms to inhibit MAVS function, thereby evading the host immune response. Research has also suggested a potential link between MAVS and certain autoimmune diseases, where an overactive immune response may be detrimental.

Interactions

MAVS interacts with several proteins involved in the antiviral signaling pathway, including:

• RIG-I
• MDA5
• TRAF3
• TRAF6
• TBK1
• IKKε

These interactions are crucial for the propagation of the antiviral signal and the subsequent activation of the immune response.

Research and Therapeutic Potential

Given its central role in antiviral immunity, MAVS is a target of interest for therapeutic interventions aimed at enhancing antiviral responses or modulating immune activity in autoimmune diseases. Ongoing research is focused on understanding the detailed mechanisms of MAVS signaling and its regulation.

See also

• Innate immune system
• Type I interferon
• RIG-I-like receptor
• NF-κB
• IRF3