Trout granulomatous virus (TGV) infection is associated with disruption of gill morphology, endothelial damage, and local gill immune responses in rainbow trout

Trout Granulomatous Virus (TGV) is an emerging viral pathogen associated with chronic infections in adult farmed rainbow trout (Oncorhynchus mykiss). TGV infection was first described to be associated with the formation of granulomas in the liver and heart of infected trout, while gill pallor was a common gross sign of the disease. The goal of the present study was to characterize the histopathological changes and immune responses that occur in the gills of farmed rainbow trout during a natural TGV infection. Histopathological examination revealed widespread damage in the gill system of clinically affected trout, characterized by hemorrhages, edema, lamellar fusion, and immune cell infiltration. Histopathology scores did not correlate with TGV gill viral loads measured by RT-qPCR. Granulomas located in the fused secondary gill lamella, the interbranchial lymphoid tissue (ILT) and the amphibranchial lymphoid tissue (ALT) were observed in an animal with high TGV loads. Immunofluorescence staining revealed that 1) TGV can infect MHC-II⁺ immune cells in the gills and liver including within granulomas; 2) MHC-II⁺ cell numbers in the gills are significantly lower in TGV⁺ compared to TGV⁻ trout; 3) gill pIgR expression is up-regulated in TGV⁺ compared to TGV⁻ trout; 4) Clinically affected trout show unusual gill IgM expression patterns. Our results uncover the importance of the gills as a site for TGV replication and several potential mechanisms by which TGV can persist chronically in the infected trout host. Finally, local damage and immune responses do not necessarily correlate with TGV loads determined by RT-qPCR.