Abstract
Sleeping disease in rainbow trout is characterized by an abnormal swimming behaviour of the fish which stay on their side at the bottom of the tanks. This sign is due to extensive necrosis and atrophy of red skeletal muscle induced by the sleeping disease virus (SDV), also called salmonid alphavirus 2. Infections of humans with arthritogenic alphaviruses, such as Chikungunya virus (CHIKV), are global causes of debilitating musculoskeletal diseases. The mechanisms by which the virus causes these pathologies are poorly understood due to the restrictive availability of animal models capable of reproducing the full spectrum of the disease. Nevertheless, it has been shown that CHIKV exhibits a particular tropism for muscle stem cells also known as satellite cells. Thus, SDV and its host constitute a relevant model to study in details the virus-induced muscle atrophy, the pathophysiological consequences of the infection of a particular cell-type in the skeletal muscle, and the regeneration of the muscle tissue in survivors together with the possible virus persistence. To study a putative SDV tropism for that particular cell type, we established an in vivo and ex vivo rainbow trout model of SDV-induced atrophy of the skeletal muscle. This experimental model allows reproducing the full panel of clinical signs observed during a natural infection since the transmission of the virus is arthropod-borne independent. The virus tropism in the muscle tissue was studied by immunohistochemistry together with the kinetics of the muscle atrophy, and the muscle regeneration post-infection was observed. In parallel, an ex vivo model of SDV infection of rainbow trout satellite cells was developed and virus replication and persistence in that particular cell type was followed up to 73 days post-infection. These results constitute the first observation of a specific SDV tropism for the muscle satellite cells.
Highlights
Sleeping disease in salmonids has been first observed in France in [1]
In rainbow trout (Oncorhynchus mykiss), the disease is characterized by an abnormal swimming behaviour of the fish which stay on their side at the bottom of the tanks, the name “sleeping” disease
This relevant model which reproduces the full pathogenesis as observed in the field is based on the infection of juvenile rainbow trout by a
Summary
In rainbow trout (Oncorhynchus mykiss), the disease is characterized by an abnormal swimming behaviour of the fish which stay on their side at the bottom of the tanks, the name “sleeping” disease. This sign is presumably due to extensive necrosis of red skeletal muscle. A reverse genetics system has been established for SDV allowing the manipulation of the viral genome and the expression of a reporter gene [4, 12]. The experimental transmission of the disease to juvenile trout by bath immersion is well established and reproduces each lesion type observed in the field. Skeletal muscle lesions are characterized by degeneration and disappearance of fibers of the lateral line (red muscle) and adjacent white muscle with inflammation and fibrosis of supporting muscle fascia [14]
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