Preferential association of hepatitis C virus with CD19+ B cells is mediated by complement system

 

Autores
Wang, Richard; Baré, Patricia; De Giorgi, Valeria; Matsuura, Kentaro; Salam, Kazi Abdus; Grandinetti, Teresa; Schechterly, Cathy; Alter, Harvey J.
Tipo de recurso
artículo
Estado
Versión publicada
Año de publicación
2016
País
Argentina
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio
CONICET Digital (CONICET)
Descripción
Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV-related lymphoproliferative disorders is not fully understood. Recent studies have found that HCV in peripheral blood mononuclear cells (PBMCs) from chronically infected patients is mainly associated with CD19+ B cells. To further elucidate this preferential association of HCV with B cells, we used in vitro cultured virus and uninfected PBMCs from healthy blood donors to investigate the necessary serum components that activate the binding of HCV to B cells. First, we found that the active serum components were present not only in HCV carriers, but also in HCV recovered patients and HCV negative healthy blood donors and that the serum components were heat labile. Second, the preferential binding activity of HCV to B cells could be blocked by anti-complement C3 antibodies. In experiments with complement-depleted serum and purified complement proteins, we demonstrated that complement proteins C1, C2, and C3 were required to activate such binding activity. Complement protein C4 was partially involved in this process. Third, using antibodies against cell surface markers, we showed that the binding complex mainly involved CD21 (complement receptor 2), CD19, CD20, and CD81; CD35 (complement receptor 1) was involved but had lower binding activity. Fourth, both anti-CD21 and anti-CD35 antibodies could block the binding of patient-derived HCV to B cells. Fifth, complement also mediated HCV binding to Raji cells, a cultured B cell line derived from Burkitt´s lymphoma.CONCLUSION:In chronic HCV infection, the preferential association of HCV with B cells is mediated by the complement system, mainly through complement receptor 2 (CD21), in conjunction with the CD19 and CD81 complex. This article is protected by copyright. All rights reserved.
Idioma
inglés
OAI Identifier
oai:ri.conicet.gov.ar:11336/45019
Enlace del recurso
http://hdl.handle.net/11336/45019
Nivel de acceso
Acceso abierto
Materia
HEPATITIS C
LEUCOCYTES
B-LIMPHOCYTES
CD19
HEPACIVIRUS
Bioquímica y Biología Molecular
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Patología
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD