Infection of myofibers contributes to increased pathogenicity during infection with an epidemic strain of Chikungunya virus
Autor(es): Rohatgi Anjali, Corbo Joseph C, Monte Kristen, Higgs Stephen, Vanlandingham Dana L, Kardon Gabrielle, Lenschow Deborah J
Resumo: Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes that is known to cause severe arthritis - myositis in affected patients. The ongoing epidemic began in eastern Africa in 2004 - then spread to isl-s of the Indian Ocean, India, - Southeast Asia, ultimately afflicting millions. During this outbreak, more severe disease manifestations, including fatalities, have been documented. The reasons for this change in pathogenesis are multifactorial but likely include mutations that have arisen in the viral genome which could alter disease pathogenesis. To test this hypothesis, we used a murine model of CHIKV to compare the disease pathogeneses of two recombinant strains of CHIKV, the first derived from the La Reunion outbreak in 2006 (LR2006 OPY1) - the second isolated from Senegal in 1983 (37997). While the two strains exhibited similar growth in mammalian cells in vitro, we observed more severe clinical disease - pathology in mice infected with the LR2006 OPY1 strain of CHIKV, which included prolonged viremia - elevated viral titers - persistence in the muscle, resulting in devastating myonecrosis. Both CHIKV strains infected connective tissue fibroblasts of the muscle, but only the LR2006 OPY1 strain replicated within myofibers in vivo, despite similar growth of the two strains in these cell types in vitro. However, when the 37997 strain was administered directly into muscle, myofiber infection was comparable to that in LR2006 OPY1-infected mice. These results indicate that differences in the ability of the strain of CHIKV to establish infection in myofibers may contribute to the increased disease severity. CHIKV is an emerging pathogen that causes significant morbidity. Little is known about the pathogenesis of the disease, - this study suggests that the ability of a recent epidemic strain to infect myofibers results in increased disease severity. Better underst-ing of how CHIKV causes disease contributes to the ultimate goal of creating therapeutics to alleviate the impact of this debilitating virus.
Imprenta: Journal of Virology, v. 88, n. 5, p. 2414-2425, 2014
Identificador do objeto digital: 10.1128/JVI.02716-13
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Genome ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic
Data de publicação: 2014
