Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection

PLOS ONE, Jun 2007

Background Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. Methodology/Principal Findings Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. Conclusions/Significance This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans.

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Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection

et al (2007) Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection. PLoS ONE 2(6): e527. doi:10.1371/journal.pone.0000527 Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection Simona Ozden 0 1 2 Michel Huerre 0 1 2 Jean-Pierre Riviere 0 1 2 Lark L. Coffey 0 1 2 Philippe V. Afonso 0 1 2 Vincent Mouly 0 1 2 Jean de Monredon 0 1 2 Jean-Christophe Roger 0 1 2 Mohamed El Amrani 0 1 2 Jean-Luc Yvin 0 1 2 Marie-Christine Jaffar 0 1 2 Marie-Pascale Frenkiel 0 1 2 Marion Sourisseau 0 1 2 Olivier Schwartz 0 1 2 Gillian Butler-Browne 0 1 2 Philippe Despre` s 0 1 2 Antoine Gessain 0 1 2 Pierre-Emmanuel Ceccaldi 0 1 2 0 Funding: P.V.A. is a recipient from the French Minsitry of Research. This work is supported by the Association Franc aise contre les Myopathies, the University Pierre-et-Marie Curie, the Centre National de la Recherche Scientifique, the ANR/ MIME, INSERM, MYORES Network of Excellence from the European Commission (6thFP; contract 511978), and the Programmme Transversal de Recherches ''Chikungunya'' of the Pasteur Institute 1 Academic Editor: Linqi Zhang, AIDS Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College , China 2 1 Unite Epide miologie et Physiopathologie des Virus Oncoge`nes-CNRS URA1930, Institut Pasteur, Paris, France, 2 Unite Recherche et Expertise Histotechnologie et Pathologie, Institut Pasteur, Paris, France, 3 Service d'Anatomopathologie, CHD Fe lix Guyon, Saint-Denis de la Re union, France, 4 Unite Interactions Mole culaires Flavivirus-H otes, Institut Pasteur, Paris, France, 5 Inserm U787-Universite Pierre et Marie Curie-Institut de Myologie, Pitie Salpe tri e`re, Paris, France, 6 Service de Neurologie, CHD Fe lix Guyon, Saint-Denis de la Re union, France, 7 Service de Me decine Interne, CHD Fe lix Guyon, Saint-Denis de la Re union, France, 8 Laboratoire de Biologie, CHD Fe lix Guyon, Saint-Denis de la Re union, France, 9 Unite Virus et Immunite , Institut Pasteur , Paris , France Background. Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. Methodology/Principal Findings. Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. Conclusions/Significance. This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans. - INTRODUCTION Chikungunya virus (CHIKV) is a moquito-transmitted alphavirus belonging to the family Togaviridae, which was first reported in 1952 in Tanganyika. It is responsible for an acute infection of abrupt onset, characterised by high fever, arthralgia, myalgia, head-ache, chills, photophobia and rash [1]. The symptoms are generally of short duration (one week) and recovery is often complete, although some patients have recurrent episodes for several weeks after infection[1,2]. This virus is endemic in Africa, India and South-East Asia and is transmitted by Aedes mosquitoes through an urban or sylvatic transmission cycle. CHIK virus has massively emerged in the Indian Ocean, with more than 200.000 cases being reported in the Reunion island by March 2006 [3], and more than 1.25 million suspected cases in India between February and August, 2006 [4]. More recently, imported cases of CHIK virus infection have been observed in France, Germany, Switzerland and Norway [5]. From a clinical point of view, the Reunion outbreak was characterized by an atypical magnitude and virulence, with painful and invalidating poly-arthralgia, and with myalgia being reported as a major clinical symptom (97.7% of cases) [6]. A recent clinical study has reported an occurrence of rhabdomyolysis with high creatine phosphokinase (CPK) [7]. Little is known about the pathophysiological mechanisms of CHIK virus infection, and especially about the cellular targets of CHIK virus. We investigated the possible involvement of muscle cells in the CHIK pathogenesis, both by an ex-vivo ap (...truncated)


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Simona Ozden, Michel Huerre, Jean-Pierre Riviere, Lark L. Coffey, Philippe V. Afonso, Vincent Mouly, Jean de Monredon, Jean-Christophe Roger, Mohamed El Amrani, Jean-Luc Yvin, Marie-Christine Jaffar, Marie-Pascale Frenkiel, Marion Sourisseau, Olivier Schwartz, Gillian Butler-Browne, Philippe Desprès, Antoine Gessain, Pierre-Emmanuel Ceccaldi. Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection, PLOS ONE, 2007, Volume 2, Issue 6, DOI: 10.1371/journal.pone.0000527