Characterization of specific antibodies against cytomegalovirus (CMV)-encoded interleukin 10 produced by 28 % of CMV-seropositive blood donors

Author:

de Lemos Rieper Carina12,Galle Pia1,Pedersen Bente Klarlund1,Hansen Morten Bagge2

Affiliation:

1. The Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

2. Department of Clinical Immunology, Rigshospitalet, National University Hospital, Copenhagen, Denmark

Abstract

Cytomegalovirus (CMV) has evolved multiple immunological evasion strategies, including the encoding of viral interleukin (IL)-10 homologues (cmvIL-10). In this study, cmvIL-10 bound avidly to the same receptors on blood mononuclear cells and was as bio-potent as native human IL-10. Seventeen percent of plasma samples from 3200 Danish blood donors (corresponding to 28 % of the anti-CMV IgG-positive donors) contained substantial levels of anti-cmvIL-10 IgG antibodies, as measured by a radioimmunoassay for human anti-cmvIL-10 antibodies. The antibodies neither cross-reacted with native human IL-10 nor with Epstein–Barr virus-encoded IL-10. Anti-cmvIL-10 antibodies potently inhibited the binding of cmvIL-10 to cellular receptors, and they specifically inhibited cmvIL-10-induced JAK–STAT signalling. Ultimately, anti-cmvIL-10 antibodies blocked the inhibitory effect of cmvIL-10 on lipopolysaccharide-induced tumour necrosis factor alpha and IL-1β from blood mononuclear cells. Taken together, our data signify that cmvIL-10 has been produced during CMV infection, and that anti-cmvIL-10 IgG antibodies represent an effective immunological counter reaction against cmvIL-10.

Publisher

Microbiology Society

Subject

Virology

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