Contributions
Abstract: EP1499
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 16 Microbiology and Virology
Background: Whereas the exact pathogenesis of multiple sclerosis (MS) is still not understood, it is generally accepted that MS results from an interplay of genetic and environmental factors. The strongest genetic risk factor for MS is the human leukocyte antigen (HLA) class II allele HLA-DRB1*15:01. The strongest environmental risk factor for MS is infection with the B lymphocytotropic herpesvirus Epstein-Barr Virus (EBV). Although it is well-known that EBV uses HLA-DQ, -DR and -DP as co-receptors for infection of B cells, it was hitherto unknown whether HLA-DRB1*15:01 may act as a co-receptor for EBV infection.
Objective: To investigate whether HLA-DRB1*15:01 confers susceptibility to EBV infection to a B cell line in vitro.
Methods: We transfected the HLA-DR deficient B lymphoblastoid cell line 721.174 (LCL721.174) with plasmids expressing HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*11:01 and DRB1*01:01 and subsequently infected these cells with a recombinant EBV encoding green fluorescent protein (EBV-GFP). The percentage of EBV-infected cells (i.e. GFP-positive cells) among HLA-DR expressing cells was determined by flow cytometry.
Results: While untransfected LCL721.174 and LCL721.174 transfected with an empty vector were not infectable with EBV-GFP, transfection with HLA-DRB1*15:01 conferred susceptibility to EBV infection to LCL721.174. There was a trend for a higher percentage of EBV-infected LCL721.174 among HLA-DRB1*15:01 compared to HLA-DRB1*13:03, HLA-DRB1*11:01 and DRB1*01:01 expressing LCL721.174 (p=0.2, Kruskal-Wallis test).
Conclusion: Our findings show that EBV uses HLA-DRB1*15:01 as a co-receptor for infection of B cells in vitro, pointing towards a potential mechanistic link between the strongest genetic and environmental risk factors for MS. Future studies should clarify how different HLA class II alleles influence the susceptibility of B cells to EBV infection in vivo.
Disclosure:
JM: Nothing to disclose
FG: Nothing to disclose
KR: Received research support from Novartis, Merck Serono and the German Ministry for Education and Research (BMBF/KKNMS; Competence Network Multiple Sclerosis), as well as speaking fees or travel grants from Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche, Novartis, and the Guthy-Jackson Charitable Foundation.
Abstract: EP1499
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 16 Microbiology and Virology
Background: Whereas the exact pathogenesis of multiple sclerosis (MS) is still not understood, it is generally accepted that MS results from an interplay of genetic and environmental factors. The strongest genetic risk factor for MS is the human leukocyte antigen (HLA) class II allele HLA-DRB1*15:01. The strongest environmental risk factor for MS is infection with the B lymphocytotropic herpesvirus Epstein-Barr Virus (EBV). Although it is well-known that EBV uses HLA-DQ, -DR and -DP as co-receptors for infection of B cells, it was hitherto unknown whether HLA-DRB1*15:01 may act as a co-receptor for EBV infection.
Objective: To investigate whether HLA-DRB1*15:01 confers susceptibility to EBV infection to a B cell line in vitro.
Methods: We transfected the HLA-DR deficient B lymphoblastoid cell line 721.174 (LCL721.174) with plasmids expressing HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*11:01 and DRB1*01:01 and subsequently infected these cells with a recombinant EBV encoding green fluorescent protein (EBV-GFP). The percentage of EBV-infected cells (i.e. GFP-positive cells) among HLA-DR expressing cells was determined by flow cytometry.
Results: While untransfected LCL721.174 and LCL721.174 transfected with an empty vector were not infectable with EBV-GFP, transfection with HLA-DRB1*15:01 conferred susceptibility to EBV infection to LCL721.174. There was a trend for a higher percentage of EBV-infected LCL721.174 among HLA-DRB1*15:01 compared to HLA-DRB1*13:03, HLA-DRB1*11:01 and DRB1*01:01 expressing LCL721.174 (p=0.2, Kruskal-Wallis test).
Conclusion: Our findings show that EBV uses HLA-DRB1*15:01 as a co-receptor for infection of B cells in vitro, pointing towards a potential mechanistic link between the strongest genetic and environmental risk factors for MS. Future studies should clarify how different HLA class II alleles influence the susceptibility of B cells to EBV infection in vivo.
Disclosure:
JM: Nothing to disclose
FG: Nothing to disclose
KR: Received research support from Novartis, Merck Serono and the German Ministry for Education and Research (BMBF/KKNMS; Competence Network Multiple Sclerosis), as well as speaking fees or travel grants from Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche, Novartis, and the Guthy-Jackson Charitable Foundation.