(Uploaded by Plazi for the Bat Literature Project) The 2'-5' oligoadenylate synthetase (OAS) family consist of three genes encoding active OAS enzymes (OAS1-3) and an OAS-Like (OASL) gene encoding an inactive protein. The transcription of all four members of this family is actively induced by interferon (IFN), but so far no attempt to systematically analyze the expression of these genes during viral infection has been made. We analyzed the expression of the human OAS1 and OASL genes in response to infection with Sendai virus or Influenza A virus. Surprisingly, we found a marked difference in the expression pattern of these genes. Our data showed that the OASL gene is rapidly induced in response to viral infection and that this induction is mediated by IFN regulatory factor 3 (IRF-3). In contrast to the OASL gene, the induction of the OAS1 gene by virus infection was lower, and did require a functional type I IFN response. The pronounced difference in gene regulation between the OAS1 and OASL genes agrees with a functional difference between these genes, which must exist as a consequence of the lack of the 2-5A synthetase activity of the OASL protein. Furthermore, the behavior of the OASL gene is consistent with the behavior of an antiviral gene.