2'-5'-oligoadenylate synthase

2'-5'-Oligoadenylate Synthase

2'-5'-Oligoadenylate synthase (OAS) is an enzyme that plays a crucial role in the innate immune response to viral infections. It is part of the interferon-induced antiviral pathway and is responsible for the synthesis of 2'-5'-linked oligoadenylates (2-5A) from adenosine triphosphate (ATP). These oligoadenylates activate RNase L, an endoribonuclease that degrades viral and cellular RNA, thereby inhibiting viral replication.

Structure and Function

OAS is a family of enzymes that includes several isoforms, such as OAS1, OAS2, and OAS3, which differ in their size and oligomerization state. These enzymes are activated by double-stranded RNA (dsRNA), a molecular pattern associated with viral infections. Upon activation, OAS catalyzes the formation of 2'-5'-linked oligoadenylates, which are unusual because most biological nucleic acids are linked by 3'-5' phosphodiester bonds.

The 2-5A molecules bind to and activate RNase L, leading to the degradation of both viral and host RNA. This process is part of the broader antiviral response mediated by type I interferons, which are cytokines that enhance the expression of antiviral proteins.

Biological Significance

The OAS/RNase L pathway is a critical component of the host defense against viral infections. It is particularly important in the response to RNA viruses, such as influenza virus, hepatitis C virus, and coronavirus. The pathway not only limits viral replication but also modulates the immune response by influencing the production of cytokines and other signaling molecules.

Mutations or polymorphisms in the OAS genes have been associated with susceptibility to viral infections and autoimmune diseases. For example, certain variants of OAS1 have been linked to increased risk of SARS-CoV-2 infection and severity of COVID-19.

Clinical Implications

Understanding the OAS pathway has implications for the development of antiviral therapies. Modulating the activity of OAS or RNase L could enhance the antiviral response or mitigate excessive inflammation. Additionally, OAS activity can serve as a biomarker for the effectiveness of interferon-based therapies in treating viral infections.

Also see

• Interferon
• RNase L
• Innate immune system
• Antiviral drug
• Cytokine