Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
Cell Rep. 2023 Jun 27;42(6):112597. doi: 10.1016/j.celrep.2023.112597. Epub 2023 Jun 7.
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.
鼠巨细胞病毒（MCMV）感染巨噬细胞依赖于 MCMV 编码的趋化因子 2（MCK2），而感染成纤维细胞则不依赖于 MCK2。最近，发现 MCMV 对这两种细胞类型的感染都依赖于细胞表达的神经纤毛蛋白 1。通过 CRISPR 筛选，我们现在确定 MCK2 依赖性感染需要 MHC Ⅰ类/β-2-微球蛋白（B2m）的表达。进一步的分析表明，表达 MHC Ⅰ类 haplotypes H-2b 和 H-2d 的巨噬细胞，但不是 H-2k，容易受到 MCMV 依赖于 MCK2 的感染。B2m 缺陷小鼠缺乏 MHC Ⅰ类分子的表面表达，实验表明 MHC Ⅰ类表达对于 MCK2 依赖性原发性感染和病毒传播非常重要。在这些小鼠中，鼻腔内给予 MCK2 有效的 MCMV 模拟了野生型小鼠中 MCK2 缺陷型 MCMV 的感染模式：它不会感染肺泡巨噬细胞，随后也不会传播到唾液腺。这些数据为理解 MCMV 诱导的发病机制、组织靶向和病毒传播提供了必要的知识。
