Piscine reovirus encodes a cytotoxic, non-fusogenic, integral membrane protein and previously unrecognized virion outer-capsid proteins

Abstract

Piscine reovirus (PRV) is a tentative new member of the family Reoviridae and has been linked to heart and skeletal muscle inflammation in farmed Atlantic salmon (Salmo salar L.). Recent sequence-based evidence suggests that PRV is about equally related to members of the genera Orthoreovirus and Aquareovirus. Sequence similarities have also suggested that PRV might encode a fusion-associated small transmembrane (FAST) protein, which in turn suggests that PRV might be the prototype of a new genus with syncytium-inducing potential. In previous support of this designation has been the absence of identifiable PRV-encoded homologues of either the virion outer-clamp protein of ortho-and aquareoviruses or the virion outer-fibre protein of most orthoreoviruses. In the current report, we have provided experimental evidence that the putative p13 FAST protein of PRV lacks the defining feature of the FAST protein family -the ability to induce syncytium formation. Instead, p13 is the first example of a cytosolic, integral membrane protein encoded by ortho-or aquareoviruses, and induces cytotoxicity in the absence of cell-cell fusion. Sequence analysis also identified signature motifs of the outer-clamp and outer-fibre proteins of other reoviruses in two of the predicted PRV gene products. Based on these findings, we conclude that PRV does not encode a FAST protein and is therefore unlikely to be a new fusogenic reovirus. The presence of a novel integral membrane protein and two previously unrecognized, essential outer-capsid proteins has important implications for the biology, evolution and taxonomic classification of this virus.

Full-Genome Sequencing and Confirmation of the Causative Agent of Erythrocytic Inclusion Body Syndrome in Coho Salmon Identifies a New Type of Piscine Orthoreovirus

“…PRV-2 encodes homologues of all the genes that are found in PRV (λ1, λ2, λ3, μ1, μ2, μNS, σ1, σ2, σ3, σNS, and p13). Previous studies have suggested that the presence of an integral membrane protein, p13, and two essential outer capsid proteins, σ3 and σ1, has important implications for the unique evolution and taxonomic classification of PRV [22, 26, 27]. In PRV, the p13 membrane protein is encoded on the same segment as the σ3 protein, in a bicistronic segment, whereas the σ1 protein is encoded on a monocistronic segment, rather than on a bi- or tricistronic segment [22, 26, 27].…”

Bioinformatics of Recent Aqua- and Orthoreovirus Isolates from Fish: Evolutionary Gain or Loss of FAST and Fiber Proteins and Taxonomic Implications

“…GCRV-HZ08/GD108 and GCRV104 possess the 11-segment profile of approved Aquareovirus members, whereas PRV has the 10-segment profile of approved Orthoreovirus members. We have recently reported that PRV is also like some orthoreoviruses, and unlike approved aquareoviruses, in encoding an outer-fiber protein, p35, and also in not encoding an NS-FAST protein [32] (Tables 1, 2, and S1). The additional NS protein encoded by PRV, p13, is instead a cytotoxic integral-membrane protein that localizes to cytosolic compartments, not to the plasma membrane as do FAST proteins.…”

Virus genomes and virus-host interactions in aquaculture animals

“…Scophthalmus maximus reovirus, a novel reovirus isolated from marine fish, contains a FAST protein translated from a non-AUG start site that has been shown to partially contribute to the cytopathic effect caused by infection with this virus [94]. As a new reovirus equally related to members of the Orthoreovirus and Aquareovirus genera, Piscine reovirus, which is linked to heart and skeletal muscle inflammation in farmed Atlantic salmon (Salmo salar L.), has been suggested by whole genome comparisons to be more closely related to orthoreoviruses and, therefore, a new species of the Orthoreovirus genus [96]. Genome comparisons show that Piscine reovirus contains 10 genomic segments (not 11 as in all recognized aquareoviruses) and an outer-fiber protein that is present in most members of the Orthoreovirus genus [96,97].…”

“…As a new reovirus equally related to members of the Orthoreovirus and Aquareovirus genera, Piscine reovirus, which is linked to heart and skeletal muscle inflammation in farmed Atlantic salmon (Salmo salar L.), has been suggested by whole genome comparisons to be more closely related to orthoreoviruses and, therefore, a new species of the Orthoreovirus genus [96]. Genome comparisons show that Piscine reovirus contains 10 genomic segments (not 11 as in all recognized aquareoviruses) and an outer-fiber protein that is present in most members of the Orthoreovirus genus [96,97]. Moreover, phylogenetic evidence of long distance dispersal and transmission has been revealed by comparing the protein coding sequences S1, S2 and S4 in Piscine reovirus genomic segments between farmed and wild Atlantic salmon [98].…”