title: Establishment of a Novel Primary Human Skeletal Myoblast Cellular Model for Chikungunya Virus Infection and Pathogenesis.
abstract: Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia and is now considered endemic in countries across Asia and Africa. The tissue tropism of CHIKV infection in humans remains, however, ill-defined. Due to the fact that myositis is commonly observed in most patients infected with CHIKV, we sought to develop a clinically relevant cellular model to better understand the pathogenesis of CHIKV infection. In this study, primary human skeletal muscle myoblasts (HSMM) were established as a novel human primary cell line that is highly permissive to CHIKV infection, with maximal amounts of infectious virions observed at 16 hours post infection. Genome-wide microarray profiling analyses were subsequently performed to identify and map genes that are differentially expressed upon CHIKV infection. Infection of HSMM cells with CHIKV resulted in altered expressions of host genes involved in skeletal- and muscular-associated disorders, innate immune responses, cellular growth and death, host metabolism and virus replication. Together, this study has shown the establishment of a clinically relevant primary human cell model that paves the way for the further analysis of host factors and their involvement in the various stages of CHIKV replication cycle and viral pathogenesis.
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Khairunnisa' Mohamed
authors.initials: KM
authors.lastname: Hussain
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Regina Ching Hua
authors.initials: RC
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Mary Mah-Lee
authors.initials: MM
authors.lastname: Ng
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
authors.forename: Justin Jang Hann
authors.initials: JJ
authors.lastname: Chu
mesh_terms: D017209:Apoptosis; D065632:Chikungunya Fever / Q000235:genetics / Q000821:virology*; D002646:Chikungunya virus / Q000502:physiology* / Q000648:ultrastructure; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D032448:Myoblasts, Skeletal / Q000378:metabolism* / Q000821:virology*; D061251:Primary Cell Culture; D015203:Reproducibility of Results; D056189:Viral Tropism; D014779:Virus Replication