Salmon AlphaVirus (SAV) is the aetiological agent of Salmon Pancreas Disease (SPD), a serious disease in farmed Atlantic salmon. Currently there is no available information on the ability of this virus to stimulate or suppress aspects of innate immunity in host cells. Two different Atlantic salmon cell lines (SHK-1 and TO), both derived from head kidney leucocytes, were infected with SAV and the kinetics and magnitude of gene expression were studied by real-time quantitative PCR. SAV nsP1 gene transcripts for strain P42P increased rapidly in TO cells with subsequent development of a cytopathic effect (CPE) while this virus strain hardly replicated at all SHK-1 cells causing no CPE. SAV P42P induced strong expression of type I IFN (IFN) and the antiviral IFN-induced gene MX transcripts in SHK-1 cells. Although the IFN response in infected TO cells was higher than in SHK-1 cells, the level of MX transcripts was lower. This may be because the virus was able to interfere with IFN-signaling and suppress MX transcription or that the TO cells are less able to transcribe the MX gene. Either way, it may account for why the SHK-1 cells suppress SAV replication while the TO cells are highly susceptible and succumb to the virus. The present results provide the first evidence for differential induction of expression of the interferon-induced antiviral gene, MX, correlating with resistant (SHK-1) and susceptible (TO) Atlantic salmon cell lines in response to infection by SAV.