MCK2-mediated MCMV infection of macrophages and virus dissemination to the salivary gland depends on MHC class I molecules
| Autor: | Berislav Bošnjak, Elisa Henze, Yvonne Lueder, Kim Thi Hoang Do, Alaleh Rezalotfi, Berislav Čuvalo, Christiane Ritter, Anja Schimrock, Stefanie Willenzon, Hristo Georgiev, Lea Fritz, Melanie Galla, Karen Wagner, Martin Messerle, Reinhold Förster |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Cell Reports, Vol 42, Iss 6, Pp 112597- (2023) |
| Druh dokumentu: | article |
| ISSN: | 2211-1247 06789684 |
| DOI: | 10.1016/j.celrep.2023.112597 |
| Popis: | Summary: 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/β-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 expression 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 pathogenesis, tissue targeting, and virus dissemination. |
| Databáze: | Directory of Open Access Journals |
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