Abstract
Viral hemorrhagic septicemia virus (VHSV) infection appears to be halted in rainbow trout nucleated red blood cells (RBCs). Diverse mechanisms are thought to be related to the antiviral immune response of rainbow trout RBCs to VHSV. However, the specific rainbow trout RBC proteins that interact directly with VHSV are still unknown. In an attempt to identify VHSV-RBC protein interactions, we characterized the immunoprecipitated (IP) proteome of RBCs exposed to VHSV using an antibody against the N protein of VHSV. The IP proteomic characterization identified 31 proteins by mass spectrometry analysis. Among them, we identified interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), a protein belonging to a family of proteins that are induced after the production of type I interferon. Importantly, IFIT5 has been implicated in the antiviral immune response. We confirmed the participation of IFIT5 in the rainbow trout RBC antiviral response by examining the expression profile of IFIT5 in RBCs after VHSV exposure at transcriptional and protein levels. We detected a correlation between the highest IFIT5 expression levels and the decline in VHSV replication at 6 h post-exposure. In addition, silencing ifit5 resulted in a significant increase in VHSV replication in RBCs. Moreover, an increase in VHSV replication was observed in RBCs when the IFIT5 RNA-binding pocket cavity was modulated by using a natural compound from the SuperNatural II database. We performed a proximity ligation assay and detected a significant increase in positive cells among VHSV-exposed RBCs compared to unexposed RBCs, indicating protein-protein colocalization between IFIT5 and the glycoprotein G of VHSV. In summary, these results suggest a possible role of IFIT5 in the antiviral response of RBCs against VHSV.
Highlights
The role of nucleated red blood cells (RBCs) as immune response cell mediators has become clearer in recent years
Several mechanisms have been suggested to be involved in the antiviral response of rainbow trout RBCs to Viral hemorrhagic septicemia virus (VHSV), such as increased protein levels of β-defensin 1 (BD1, an antimicrobial peptide involved in antiviral innate immunity), global protein synthesis inhibition corresponding to a virus and host cell shut-off, or an antioxidantrelated antiviral response [4]
It was recently reported that VHSV infection appeared to be halted in rainbow trout RBCs [4]
Summary
The role of nucleated red blood cells (RBCs) as immune response cell mediators has become clearer in recent years. Recent studies have demonstrated that RBCs halt viral hemorrhagic septicemia rhabdovirus (VHSV) infection [4]. Several mechanisms have been suggested to be involved in the antiviral response of rainbow trout RBCs to VHSV, such as increased protein levels of β-defensin 1 (BD1, an antimicrobial peptide involved in antiviral innate immunity), global protein synthesis inhibition corresponding to a virus and host cell shut-off, or an antioxidantrelated antiviral response [4]. An increase in the expression of IFN-related genes and proteins, such as Mx, has been observed in infectious pancreatic necrosis virus-exposed RBCs, where the viral infection was non-productive [7]
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