HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells
Qingxue Li, Wei Bu, Erin Gabriel, Fiona Aguilar, Yo Hoshino, Hiroko Miyadera, Christoph Hess, Ronald L. Hornung, Amitava Roy, Jeffrey I. Cohen
Qingxue Li, Wei Bu, Erin Gabriel, Fiona Aguilar, Yo Hoshino, Hiroko Miyadera, Christoph Hess, Ronald L. Hornung, Amitava Roy, Jeffrey I. Cohen
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Research Article Virology

HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells

Abstract

Epstein-Barr virus (EBV) infects B cells and ~95% of adults are infected. EBV glycoprotein gp42 is essential for entry of virus into B cells. EBV gp42 binds to the β1 chain of HLA-DQ, -DR, and -DP on B cells, and uses these molecules for infection. To investigate if certain HLA-DQ alleles are associated with EBV seronegativity, we recruited ~3,300 healthy adult blood donors, identified 106 EBV-seronegative individuals, and randomly selected a control group of EBV-seropositive donors from the donor pool. A larger than expected proportion of EBV-seronegative subjects were HLA-DQ β1 *04/*05 and *06/*06, and to a lesser extent, *02/*03, compared with the control group, while a larger than expected portion of EBV-seropositive persons were HLA-DQ β1 *02/*02. We examined the ability of EBV gp42 to bind to different HLA-DQ molecules using human and mouse cells stably expressing these alleles. EBV gp42 bound less effectively to cells expressing HLA-DQ β1 *04/*05, *06/*06, or *03/*03 than to cells expressing HLA-DQ β1 *02/*02. These data are consistent with our observations of increased EBV seronegativity with DQ β1 *04/*05 or *06/*06 alleles. These findings emphasize the importance of a single genetic locus (HLA-DQ β1) to influence infectivity with EBV.

Authors

Qingxue Li, Wei Bu, Erin Gabriel, Fiona Aguilar, Yo Hoshino, Hiroko Miyadera, Christoph Hess, Ronald L. Hornung, Amitava Roy, Jeffrey I. Cohen

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Figure 4

Cells expressing HLA-DQ β1 *02/*02 bind more gp42 than cells expressing DQ*03/*03 or *06/*06 when expressed independently of other HLA molecules.

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Cells expressing HLA-DQ β1 *02/*02 bind more gp42 than cells expressing ...
Mouse 3T3 cells expressing HLA-DQ αβ heterodimers were incubated with purified gp42-His followed by anti-His antibody as described in the legend to Figure 2. The amount of gp42 bound was quantified by FACS. Cell surface HLA-DQ β1 levels were also quantified in the same experiment by staining with Ia3 antibody followed by isotype-specific secondary antibody (Alexa647). The ratio of the mean fluorescence intensity (MFI) for gp42 binding (FL-4) divided by ΔMHC, which is the ratio of cell surface DQ expression to internal control GFP (24), is shown. The results were the same when we defined gp42 binding efficiency as the ratio of the MFI of gp42 binding divided by the MFI of HLA-DQ. The data were obtained from 10 independent experiments. Means (short horizontal lines) ± SEM (long horizontal lines) are shown.