Abstract
Epstein–Barr virus (EBV) is the first reported oncogenic virus and infects more than 90% of adults worldwide. EBV can establish a latent infection in B lymphocytes which is essential for persistence and transmission. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into a B cell. The N-terminal region of gp42 plays a key role in binding to gH/gL and triggering subsequent membrane fusion. However, no antibody has been reported to recognize this region and the immunogenicity of gp42 N-domain remains unknown. In the present study, we have generated a panel of nine mAbs against the gp42 N-terminal region (six mAbs to gp42-44-61aa and three mAbs to gp42-67-81aa). These mAbs show excellent binding activity and recognize different key residues locating on the gp42 N-domain. Among the nine mAbs, 4H7, 4H8 and 11G10 cross-react with rhLCV-gp42 while other mAbs specifically recognize EBV-gp42. Our newly obtained mAbs provide a useful tool for investigating the gp42 function and viral infection mechanism of γ-Herpesvirus. Furthermore, we assess the immunogenicity of the gp42 N-terminal region using the HBc149 particle as a carrier protein. The chimeric VLPs can induce high antibody titers and elicit neutralizing humoral responses to block EBV infection. More rational and effective designs are required to promote the gp42-N terminal region to become an epitope-based vaccine.
Highlights
Epstein–Barr virus (EBV), called Human Herpesvirus 4 (HHV-4), is a member of the human herpesvirus family and belongs to the gammaherpesvirus sub-family [1,2]
B cell infection requires an additional glycoprotein, gp42, which binds to a B cell receptor, human leukocyte antigen (HLA) class II, through its C-type lectin domain (CTLD) [7,8]. gp42 is a unique glycoprotein to EBV and gp42 deleted virus can bind to B cells while it loses the ability to infect B cells, implying that gp42 is indispensable for B cell infection [2,9]
We have focused on the gp42 N-terminal region and generated a panel of monoclonal antibody (mAb) targeting residues 44-61 and 67-81, respectively
Summary
Epstein–Barr virus (EBV), called Human Herpesvirus 4 (HHV-4), is a member of the human herpesvirus family and belongs to the gammaherpesvirus sub-family [1,2]. B cell infection requires an additional glycoprotein, gp, which binds to a B cell receptor, human leukocyte antigen (HLA) class II, through its C-type lectin domain (CTLD) [7,8]. We have focused on the gp N-terminal region and generated a panel of mAbs targeting residues 44-61 and 67-81, respectively. These nine mAbs show high affinity with gp and can be used in an enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence (IF) and surface plasmon resonance (SPR), which are useful tools for investigating EBV infection mechanisms. The immunogenicity analysis demonstrates that the gp N-terminal region could induce sufficient neutralizing antibody titer to prevent EBV infection. This is the first systematic analysis of immunogenicity of the gp N-terminal region
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