Following the unprecedented magnitude outbreak of CHIK virus in La Réunion
in 2005, the present work constitutes the first anatomopathological report of myositis associated with CHIK virus infection in humans. Although the expression patterns of the few (patient#1) or numerous (patient#2) infiltrating cells is not specific and is consistent with a diagnosis of viral myositis such as Coxsackie virus
, these results constitute the first observation of a selective viral infection of muscle satellite cells in humans. Muscle satellite cells are myogenic precursor cells that persist in mature skeletal muscle as quiescent cells 
. They are located under the basal lamina of the muscle fiber and contribute myonuclei to growing muscle fibers by cell fusion. They are considered as the main, if not only, cell type responsible for postnatal muscle growth and repair 
. Because CHIK virus-infected cells have been observed three to four months after the acute crisis, we hypothesize that infection of precursor cells may have pathological consequences on long-term muscle physiology in patients. Consistent with this, susceptibility of satellite cells might be crucial for the physiopathology of CHIK virus infection in humans with a possible persistence of virus on muscle tissue leading to recurrent myalgia. Another conclusion of these observations is that sections from patient#2 showed more infiltrating cells (mainly macrophages and T cells) than patient#1, but less satellite cell immunoreactive for CHIK virus antigens. Since patient#2 corresponds to a more chronic stage of the disease, it can be hypothesized that some CHIK virus-infected satellite cells could be eliminated, either by a direct cytopathic effect or through the immune response.
The pathogenesis of CHIK virus infection in humans is still poorly understood. In a recent study, CHIK virus isolates from La Reunion outbreak were found to infect in vitro
human epithelial and endothelial cells, primary fibroblasts, and, to a lower extent monocyte-derived macrophages, but not primary lymphocytes and monocytes, nor monocyte-derived dendritic cells
Muscle cells have been proposed to be target cells for alphavirus infection
. Muscle necrosis has been observed during infection of both trout and salmon by alphaviruses such as Sleeping Disease Virus
. Mayaro virus has been reported to induce myalgias in humans, and muscle necrosis in animal models
. Besides these alterations, alphavirus infection of muscle has also been reported, as Ross River Virus in a mouse model
, Getah virus that infects and induces degenerative changes in myofibers
, or Semliki Forest Virus that infects murine muscle cultures
. However, these studies were either performed on animal models, or only based on clinical observations in man, and the cellular target of virus infection was either not identified within the muscle, or identified as muscle fibers and/or infiltrating cells.
Our experimental model based on CHIK virus infection of human satellite cells may be useful to gain insights into the regulated expression of cell surface molecules which function as CHIK virus attachment factors or receptors. Indeed, such a regulation of a receptor to an alphavirus has already been reported, on mouse brain cells that express differentially a Sindbis virus receptor during development
The ability of CHIK virus to selectively infect progenitor cells involved in muscle repair provides new keys to our understanding of the long term evolution of pathogen-induced myopathies through necrosis, defects in muscle regeneration, and possibly the role of a viral reservoir in recurrent crises. In this context, further observations especially in patients suffering from recurrent crises of myalgia would provide precious data on chronic infections and necrosis/regeneration processes within the muscle, and would help to assess the relevance of persistently infected muscle cells in CHIK virus-infected patients.