Human tetraspanin CD81 is a putative receptor for hepatitis C virus (HCV), because it has been sh... more Human tetraspanin CD81 is a putative receptor for hepatitis C virus (HCV), because it has been shown to bind 'bona fide' HCV particles. CD81, as all tetraspanins, spans the membrane four times forming two extracellular loops: a small (SEL) and a large one (LEL). We have shown previously that a recombinant form of LEL is sufficient for binding HCV through the major envelope glycoprotein E2. The role of SEL in the CD81-HCV interaction was questioned. We found that transfectants expressing LEL alone bind the recombinant HCV-E2 protein at much lower levels than cells expressing the wild type CD81. And therefore whether SEL contributes to the CD81-HCV interaction or whether it influences the expression of LEL was examined. We have found that in the absence of SEL, LEL is expressed at significantly reduced levels on the cell surface because it is retained intracellularly, while HCV-E2 still binds LEL. Our data suggest that SEL of CD81 does not mediate interaction with HCV, but contributes to optimal cell surface expression of LEL by mediating translocation of the whole CD81 molecule to the cell surface.
Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essent... more Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma, which show preferential expression of VHI family products. By analyzing immunoglobulin heavy chain usage, we addressed the question of whether or not clonal B-cell expansion occurrs in patients free of essential mixed cryoglobulinemia or non-Hodgkin lymphoma. Four hepatitis C virus-positive patients, all undergoing liver transplantation, were studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as a source of B cells. A patient with hepatocellular carcinoma and fresh blood from four healthy donors were used as negative controls. VHI family sequences were cloned and analyzed by reverse transcription-polymerase chain reaction. Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were identified in three out of four hepatitis C virus-infected patients. The clonally expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy chain gene usage. HCV infection can induce B-cell expansion with larger clonal variation. The restricted V gene usage in hepatitis C virus-associated non-Hodgkin lymphoma suggests that there may be selection mechanisms to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell populations in hepatitis C virus-infected patients.
Human tetraspanin CD81 is a putative receptor for hepatitis C virus (HCV), because it has been sh... more Human tetraspanin CD81 is a putative receptor for hepatitis C virus (HCV), because it has been shown to bind 'bona fide' HCV particles. CD81, as all tetraspanins, spans the membrane four times forming two extracellular loops: a small (SEL) and a large one (LEL). We have shown previously that a recombinant form of LEL is sufficient for binding HCV through the major envelope glycoprotein E2. The role of SEL in the CD81-HCV interaction was questioned. We found that transfectants expressing LEL alone bind the recombinant HCV-E2 protein at much lower levels than cells expressing the wild type CD81. And therefore whether SEL contributes to the CD81-HCV interaction or whether it influences the expression of LEL was examined. We have found that in the absence of SEL, LEL is expressed at significantly reduced levels on the cell surface because it is retained intracellularly, while HCV-E2 still binds LEL. Our data suggest that SEL of CD81 does not mediate interaction with HCV, but contributes to optimal cell surface expression of LEL by mediating translocation of the whole CD81 molecule to the cell surface.
Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essent... more Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma, which show preferential expression of VHI family products. By analyzing immunoglobulin heavy chain usage, we addressed the question of whether or not clonal B-cell expansion occurrs in patients free of essential mixed cryoglobulinemia or non-Hodgkin lymphoma. Four hepatitis C virus-positive patients, all undergoing liver transplantation, were studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as a source of B cells. A patient with hepatocellular carcinoma and fresh blood from four healthy donors were used as negative controls. VHI family sequences were cloned and analyzed by reverse transcription-polymerase chain reaction. Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were identified in three out of four hepatitis C virus-infected patients. The clonally expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy chain gene usage. HCV infection can induce B-cell expansion with larger clonal variation. The restricted V gene usage in hepatitis C virus-associated non-Hodgkin lymphoma suggests that there may be selection mechanisms to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell populations in hepatitis C virus-infected patients.
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