MCK2-mediated MCMV infection of macrophages and virus dissemination to the salivary gland depends on MHC class I molecules

Murine cytomegalovirus (MCMV) infection of macrophages relies on MCMV-encoded chemokine 2 (MCK2), while infection of fibroblasts occurs independently of MCK2. Recently, MCMV infection of both cell types was found to be dependent on cell-expressed neuropilin 1. Using a CRISPR screen, we now identify that MCK2-dependent infection requires MHC class Ia/b-2-microglobulin (B2m) expression. Further analyses reveal that macrophages expressing MHC class Ia haplotypes H-2b and H-2d, but not H-2k, are susceptible to MCK2-dependent infection with MCMV. The importance of MHC class I expres-sion for MCK2-dependent primary infection and viral dissemination is highlighted by experiments with B2m-deficient mice, which lack surface expression of MHC class I molecules. In those mice, intranasally administered MCK2-proficient MCMV mimics infection patterns of MCK2-deficient MCMV in wild-type mice: it does not infect alveolar macrophages and subsequently fails to disseminate into the salivary glands. Together, these data provide essential knowledge for understanding MCMV-induced pathogen-esis, tissue targeting, and virus dissemination.

Automated summary

Murine cytomegalovirus (MCMV) infection of macrophages depends on MCMV-encoded chemokine 2 (MCK2), while infection of fibroblasts is independent of MCK2. Recent research shows that both cell types require neuropilin 1 for MCMV infection. CRISPR screening identifies MHC class Ia/b-2-microglobulin (B2m) expression as necessary for MCK2-dependent infection.