Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response
Autor(es): Hoarau Jean-Jacques, Jaffar B-jee Marie-Christine, Krejbich Trotot Pascale, Das Trina, Li-Pat-Yuen Ghislaine, Dassa Bérengère, Denizot Mélanie, Guichard Elsa, Ribera Anne, Henni Tawfiq, Tallet Frank, Moiton Marie Pierre, Gauzère Bernard Alex, Bruniquet S-rine, Jaffar B-jee Zaïnoul, Morbidelli Philippe, Martigny Gérard, Jolivet Michel, Gay Frederick, Grandadam Marc, Tolou Hugues, Vieillard Vincent, Debré Patrice, Autran Brigitte, Gasque Philippe
Resumo: Alphaviruses, including Chikungunya virus (CHIKV), produce a transient illness in humans, but severe forms leading to chronic incapacitating arthralgia/arthritis have been reported by mechanisms largely ill-characterized. The pathogenesis of CHIKV was addressed in a prospective cohort study of 49 hospitalized patients from Reunion Isl- subsequently categorized into two distinct groups at 12 mo postinfection. Comprehensive analyses of the clinical - immunological parameters throughout the disease course were analyzed in either the recovered" or the "chronic" groups to identify prognostic markers of arthritis-like pathology after CHIKV disease. We found that the chronic group consisted mainly of more elderly patients (>60 y) - with much higher viral loads (up to 10(10) viruses per milliliter of blood) during the acute phase. Remarkably, a rapid innate immune antiviral response was demonstrated by robust dendritic/NK/CD4/CD8 cell activation - accompanied by a rather weak Th1/Th2 cytokine response in both groups. Interestingly, the antiviral immune response witnessed by high levels of IFN-alpha mRNA in PBMCs - circulating IL-12 persisted for months only in the chronic group. CHIKV (RNA - proteins) was found in perivascular synovial macrophages in one chronic patient 18 mo postinfection surrounded by infiltrating NK - T cells (CD4(++) but rare cytotoxic CD8). Fibroblast hyperplasia, strong angiogenesis, tissue lesions given the high levels of matrix metalloproteinase 2, - acute cell death [high cleaved poly(ADP-ribose) polymerase staining] were observed in the injured synovial tissue. These observed cellular - molecular events may contribute to chronic arthralgia/arthritis targeted by methotrexate used empirically for effective treatment but with immunosuppressive function in a context of viral persistence."
Imprenta: Journal of Immunology, v. 184, n. 10, p. 5914-5927, 2010
Identificador do objeto digital: 10.4049/jimmunol.0900255
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Immune response ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Molecular screening ; Chikungunya virus - Epidemiology ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2010
