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Publication : Cytomegalovirus subverts macrophage identity.

First Author  Baasch S Year  2021
Journal  Cell Volume  184
Issue  14 Pages  3774-3793.e25
PubMed ID  34115982 Mgi Jnum  J:334101
Mgi Id  MGI:6728418 Doi  10.1016/j.cell.2021.05.009
Citation  Baasch S, et al. (2021) Cytomegalovirus subverts macrophage identity. Cell 184(14):3774-3793.e25
abstractText  Cytomegaloviruses (CMVs) have co-evolved with their mammalian hosts for millions of years, leading to remarkable host specificity and high infection prevalence. Macrophages, which already populate barrier tissues in the embryo, are the predominant immune cells at potential CMV entry sites. Here we show that, upon CMV infection, macrophages undergo a morphological, immunophenotypic, and metabolic transformation process with features of stemness, altered migration, enhanced invasiveness, and provision of the cell cycle machinery for viral proliferation. This complex process depends on Wnt signaling and the transcription factor ZEB1. In pulmonary infection, mouse CMV primarily targets and reprograms alveolar macrophages, which alters lung physiology and facilitates primary CMV and secondary bacterial infection by attenuating the inflammatory response. Thus, CMV profoundly perturbs macrophage identity beyond established limits of plasticity and rewires specific differentiation processes, allowing viral spread and impairing innate tissue immunity.
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