The oligoadenylate synthetase-like protein enhances cellular antiviral activity through RIG-I pathway (68.3)
| Autor: | Saumendra Sarkar, Yugen Zhang, Jianzhong Zhu, Adriana Forero, Madhavi Ganapathiraju, Rune Hartmann, Carolyn Coyne |
|---|---|
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:68.3-68.3 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.68.3 |
| Popis: | Oligoadenylate Synthetases (OAS) are interferon (IFN) inducible enzymes, which contribute to the host anti-viral activity by inducing RNA degradation via classical OAS-RNaseL pathway. However, the OAS-like protein (OASL), which is strongly induced following virus infection, does not have enzymatic activity to synthesize 2’-5’ oligoadenylates. Therefore, the mechanism of the anti-viral activity of OASL has remained elusive. Here we describe the basis of anti-viral activity of OASL via its ability to modulate type I IFN induction through RIG-I pathway. OASL expressing cells show a strong anti-viral activity against a number of RNA and DNA virus infections in a RIG-I dependent manner. Expression of OASL enhances RIG-I mediated IFN induction. We show that OASL interacts with cytoplasmic viral RNA sensor RIG-I and enhance its activity through its C-terminal ubiquitin like domain. Poly ubiquitin binding to RIG-I is necessary and essential for RIG-I mediated induction of IFN. We demonstrate that following induction of OASL protein it provides the necessary poly Ub binding function of RIG-I. Furthermore, inactive RIG-I mutants, which are defective in ubiquitination and poly Ub binding can be rescued in presence of OASL. We show that OASL specifically enhances RIG-I mediated IFN induction without affecting MDA5, STING activation. Our findings suggest a novel mechanism by which OASL contributes to host anti-viral response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|