Mouse cytomegalovirus glycoprotein m153 binds a dendritic cell-surface ligand (VIR5P.1026)

Abstract

Abstract Mouse cytomegalovirus (MCMV) is a valuable model for studying virus-host interactions and mechanisms of viral immune evasion. MCMV encodes the m145 family of glycoproteins with predicted MHC-I structure. Among these, m153 is expressed on the surface of infected cells predominantly during the early phases of infection, independent of β2 microglobulin and peptide. We previously determined the X-ray structure of m153, establishing that it has an MHC-I-like fold and forms a stable non-covalent dimer. To identify immune cells that might express a ligand for m153, we constructed a reporter cell in which the extracellular domains of m153 were linked to human ζ chain driving green fluorescent protein upon activation. Using the reporter cell assay, we observed that CD11c+ splenic dendritic cells (DCs) and bone marrow DCs potently stimulate the m153 reporter cell. Further characterization of these cells by flow cytometry staining with an m153 tetramer and a battery of DC markers, as well as antibody blocking experiments, suggested several candidates for the m153 ligand. Transfectant cells and gene knockout animals are being studied to confirm the identity of these candidates. The identification of a host cell ligand for m153 should improve our understanding of mechanisms of host immune suppression during viral infection and will provide insight on the evolution of viral immune evasion.