Fish red blood cells (RBCs), are integral in several
biologic processes relevant to immunity, such as pathogen recognition, pathogen binding and clearance, and production of effector molecules and
cytokines. So far, one of the best strategies to control and prevent
viral diseases in aquaculture is
DNA immunization.
DNA vaccines (based on the rhabdoviral
glycoprotein G [
gpG] gene) have been shown to be effective against fish rhabdoviruses. However, more knowledge about the immune response triggered by
DNA immunization is necessary to develop novel and more effective strategies. In this study, we investigated the role of fish RBCs in immune responses induced by
DNA vaccines. We show for the first time that rainbow trout RBCs express
gpG of viral
hemorrhagic septicaemia virus (VHSV) (GVHSV) when transfected with the
DNA vaccine ex vivo and modulate the expression of immune genes and
proteins. Functional network analysis of transcriptome profiling of RBCs expressing GVHSV revealed changes in gene expression related to
G-protein coupled receptor (GPCR)-downstream signaling, complement activation, and RAR related orphan receptor α (RORA). Proteomic profile functional network analysis of GVHSV-transfected RBCs revealed
proteins involved in the detoxification of
reactive oxygen species,
interferon-stimulated gene 15 (ISG15)
antiviral mechanisms, antigen presentation of exogenous
peptides, and the
proteasome.
Conditioned medium of GVHSV-transfected RBCs conferred
antiviral protection and induced ifn1 and mx gene expression in RTG-2 cells infected with VHSV. In summary, rainbow trout nucleated RBCs could be actively participating in the regulation of the fish immune response to GVHSV
DNA vaccine, and thus may represent a possible carrier cells for the development of new
vaccine approaches.