Autor(es): Herrero Lara J, Sheng Kuo-Ching, Jian Peng, Taylor Adam, Her Zhisheng, Herring Belinda L, Chow Angela, Leo Yee-Sin, Hickey Michael J, Morand Eric F, Ng Lisa F P, Bucala Richard, Mahalingam Suresh

Resumo: Arthrogenic alphaviruses such as Ross River virus (RRV) - chikungunya virus (CHIKV) circulate worldwide. This virus class causes debilitating illnesses that are characterized by arthritis, arthralgia, - myalgia. In previous studies, we identified macrophage migration inhibitory factor (MIF) as a critical inflammatory factor in the pathogenesis of alphaviral diseases. The present study was undertaken to characterize the role of CD74, a cell surface receptor of MIF, in both RRV- - CHIKV-induced alphavirus arthritides. Mouse models of RRV - CHIKV infection were used to investigate the immunopathogenesis of arthritic alphavirus infection. The role of CD74 was assessed using histologic analysis, real-time polymerase chain reaction, flow cytometry, - plaque assay. In comparison to wild-type mice, CD74-/- mice developed only mild clinical features - had low levels of tissue damage. Leukocyte infiltration, characterized predominantly by inflammatory monocytes - natural killer cells, was substantially reduced in the infected tissue of CD74-/- mice, but production of proinflammatory cytokines - chemokines was not decreased. CD74 deficiency was associated with increased monocyte apoptosis, but had no effect on monocyte migratory capacity. Consistent with these findings, alphaviral infection resulted in a dose-dependent up-regulation of CD74 expression in human peripheral blood mononuclear cells, - serum MIF levels were significantly elevated in patients with RRV or CHIKV infection. CD74 appears to regulate immune responses to alphaviral infection through its effects on cellular recruitment - survival. These findings suggest that both MIF - CD74 play a critical role in mediating alphaviral disease, - blocking these factors with novel therapeutic agents could substantially ameliorate the pathologic manifestations.

Imprenta: Arthritis and Rheumatism, v. 65, n. 10, p. 2724-2736, 2013

Identificador do objeto digital: 10.1002/art.38090

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Viral infections ; Chikungunya virus - Real Time PCR ; Chikungunya Virus - Virus ; Chikungunya virus - Public health

Data de publicação: 2013

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