Aijing Liu, Qing Pan, Yue Li, Nana Yan, Jing Wang, Bo Yang, Zehua Chen, Xiaole Qi, Yulong Gao, Li Gao, Changjun Liu, Yanping Zhang, Hongyu Cui, Kai Li, Yongqiang Wang, Xiaomei Wang
J Virol. 2019 Oct 30. pii: JVI.01712-19. doi: 10.1128/JVI.01712-19
Infectious bursal disease virus (IBDV) is an important member of the Birnaviridae family, causing severe immunosuppressive disease in chickens. The major capsid VP2 protein is responsible for the binding of IBDV to the host cell and its cellular tropism. In order to find the potential interaction proteins with IBDV VP2, LC/MS assay was conducted and host protein chicken CD74 protein was identified. Here, we investigate the role of chicken CD74 in IBDV attachment. Co-immunoprecipitation assays indicated that the extracellular domain of CD74 interacted with the VP2 protein of multiple IBDV strains. Knockdown and Overexpression experiments showed that CD74 promotes viral infectivity. Confocal assay showed that CD74 overexpression allows the attachment of IBDV and subvirus-like particles (SVPs) to the cell surface of non-permissive cells, and qPCR analysis further confirmed the attachment function of CD74. Anti-CD74 antibody, soluble CD74, depletion of CD74 by small interfering RNA (siRNA), and CD74 knockdown in the IBDV-susceptible DT40 cell line significantly inhibited IBDV binding, suggesting a pivotal role of this protein in virus attachment. These findings demonstrate that CD74 is a novel important receptor for IBDV attachment to the chicken B lymphocyte cell line DT40.IMPORTANCECD74 plays a pivotal role in the correct folding and functional stability of MHC II molecules and in the presentation of antigenic peptides, acting as a regulatory factor in the antigen presentation process. In our study, we demonstrated a novel role of CD74 during IBDV infection, showing that chicken CD74 plays a significant role in IBDV binding to target B cells by interacting with the viral VP2 protein. This is the first report demonstrating that CD74 is involved as a novel attachment receptor in the IBDV life cycle in target B cells, thus contributing new insight into host-pathogen interactions.
Copyright © 2019 American Society for Microbiology.