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Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response.
J Immunol. 2010 May 15; 184(10):5914-27.JI

Abstract

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 Island subsequently categorized into two distinct groups at 12 mo postinfection. Comprehensive analyses of the clinical and 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) and 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 and 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 and circulating IL-12 persisted for months only in the chronic group. CHIKV (RNA and proteins) was found in perivascular synovial macrophages in one chronic patient 18 mo postinfection surrounded by infiltrating NK and T cells (CD4(++) but rare cytotoxic CD8). Fibroblast hyperplasia, strong angiogenesis, tissue lesions given the high levels of matrix metalloproteinase 2, and acute cell death [high cleaved poly(ADP-ribose) polymerase staining] were observed in the injured synovial tissue. These observed cellular and 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.

Authors+Show Affiliations

Biology Unit, Centre Hospitalier Régional Nord Félix-Guyon and Cyclotron Réunion Océan Indien, Université de la Réunion, St. Denis, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20404278

Citation

Hoarau, Jean-Jacques, et al. "Persistent Chronic Inflammation and Infection By Chikungunya Arthritogenic Alphavirus in Spite of a Robust Host Immune Response." Journal of Immunology (Baltimore, Md. : 1950), vol. 184, no. 10, 2010, pp. 5914-27.
Hoarau JJ, Jaffar Bandjee MC, Krejbich Trotot P, et al. Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. J Immunol. 2010;184(10):5914-27.
Hoarau, J. J., Jaffar Bandjee, M. C., Krejbich Trotot, P., Das, T., Li-Pat-Yuen, G., Dassa, B., Denizot, M., Guichard, E., Ribera, A., Henni, T., Tallet, F., Moiton, M. P., Gauzère, B. A., Bruniquet, S., Jaffar Bandjee, Z., Morbidelli, P., Martigny, G., Jolivet, M., Gay, F., ... Gasque, P. (2010). Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. Journal of Immunology (Baltimore, Md. : 1950), 184(10), 5914-27. https://doi.org/10.4049/jimmunol.0900255
Hoarau JJ, et al. Persistent Chronic Inflammation and Infection By Chikungunya Arthritogenic Alphavirus in Spite of a Robust Host Immune Response. J Immunol. 2010 May 15;184(10):5914-27. PubMed PMID: 20404278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. AU - Hoarau,Jean-Jacques, AU - Jaffar Bandjee,Marie-Christine, AU - Krejbich Trotot,Pascale, AU - Das,Trina, AU - Li-Pat-Yuen,Ghislaine, AU - Dassa,Bérengère, AU - Denizot,Mélanie, AU - Guichard,Elsa, AU - Ribera,Anne, AU - Henni,Tawfiq, AU - Tallet,Frank, AU - Moiton,Marie Pierre, AU - Gauzère,Bernard Alex, AU - Bruniquet,Sandrine, AU - Jaffar Bandjee,Zaïnoul, AU - Morbidelli,Philippe, AU - Martigny,Gérard, AU - Jolivet,Michel, AU - Gay,Frederick, AU - Grandadam,Marc, AU - Tolou,Hugues, AU - Vieillard,Vincent, AU - Debré,Patrice, AU - Autran,Brigitte, AU - Gasque,Philippe, Y1 - 2010/04/19/ PY - 2010/4/21/entrez PY - 2010/4/21/pubmed PY - 2010/7/20/medline SP - 5914 EP - 27 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 184 IS - 10 N2 - 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 Island subsequently categorized into two distinct groups at 12 mo postinfection. Comprehensive analyses of the clinical and 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) and 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 and 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 and circulating IL-12 persisted for months only in the chronic group. CHIKV (RNA and proteins) was found in perivascular synovial macrophages in one chronic patient 18 mo postinfection surrounded by infiltrating NK and T cells (CD4(++) but rare cytotoxic CD8). Fibroblast hyperplasia, strong angiogenesis, tissue lesions given the high levels of matrix metalloproteinase 2, and acute cell death [high cleaved poly(ADP-ribose) polymerase staining] were observed in the injured synovial tissue. These observed cellular and 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/20404278/Persistent_chronic_inflammation_and_infection_by_Chikungunya_arthritogenic_alphavirus_in_spite_of_a_robust_host_immune_response_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20404278 DB - PRIME DP - Unbound Medicine ER -