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Introduction The 2′-5′ Oligoadenylate Synthetase (OAS) family of proteins consist of 4 genes in humans, classical they act via production of 2′-5′ linked Oligoadenylates (2-5A), which activate RNase L and lead to the degradation of cellular and viral RNA in infected cells. However, mounting evidence suggest that this family has a more diverse role in the innate immune system. We recently demonstrated that extracellular OAS1 enters into cells and possesses a strong antiviral activity, both in vitro and in vivo, which is independent of RNase L [1] , [2] . This suggest a paracrine action of the OAS proteins. The OASL protein is unique in two ways, it lacks the characteristic enzymatic activity of the other OAS proteins and it has a C-terminal domain possessing a limited homology to ubiquitine. The OASL protein exhibit an antiviral activity in a way requiring the Ubi-like domain [3] . Methods We are using a combination of biochemistry, site directed mutagenesis and molecular modeling to understand the OAS function. Effect is measured as inhibition of viral replication (either Encephalomyocarditis virus or Vesicular stomatitis virus) by standard viral yield assays. Results We are currently investigating the mechanism behind the RNase L independent antiviral activity of OAS1 antiviral activity. Furthermore we have taken a mutagenesis approach to identify the molecular determinant of the antiviral activity of OASL. Conclusion Both the OAS1 and OASL proteins can exert antiviral activity independent of 2-5A synthesis, thus it appears that this family of proteins has a boarder role in the innate immune defense than so far realized. |
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