Infectious salmon anemia virus is a powerful inducer of key genes of the type I interferon system of Atlantic salmon, but is not inhibited by interferon

Abstract

Infectious salmon anemia virus (ISAV) is an aquatic orthomyxovirus causing disease and high mortality in farmed Atlantic salmon ( Salmo salar). The virus is thus apparently able to initiate replication without being hampered by the host's immune system. In this work we have studied the role of the type I interferon (IFN) system of Atlantic salmon in protection against ISAV. Real-time RT–PCR was used to study the expression of type I IFN and the IFN stimulated genes Mx and ISG15 in TO cells and live fish in response to infection with ISAV. The in vitro studies showed that ISAV was a powerful inducer of Mx and ISG15 genes in TO cells and that induction started relatively early during infection. In contrast, IFN transcripts were induced later than both Mx and ISG15 transcripts in the ISAV infected cells indicating that Mx and ISG15 are induced through IFN-independent pathways in the early stages of ISAV infection. A cohabitee infection trial with ISAV in Atlantic salmon resulted in high mortality, even though elevated levels of IFN, Mx and ISG15 transcripts in the head kidney and liver were observed. Immunoblotting confirmed the presence of Mx and ISG15 proteins in the liver of infected salmon. In order to evaluate whether the type I IFN system is able to inhibit replication of ISAV, TO cells were stimulated with recombinant salmon IFN-α1 (rSasaIFN-α1) and subsequently infected with virus. The rSasaIFN-α1 showed no protection of TO cells against ISAV, but full protection against IPNV. These data demonstrate that key proteins of the type I IFN system are induced during an ISAV infection, but that they are unable to inhibit the replication of ISAV in vitro and in vivo. ISAV must thus encode genes that enable the virus to counteract IFN induced antiviral proteins of the host.