First Author | Engels R | Year | 2022 |
Journal | Cell Rep | Volume | 38 |
Issue | 3 | Pages | 110279 |
PubMed ID | 35045303 | Mgi Jnum | J:322574 |
Mgi Id | MGI:6879567 | Doi | 10.1016/j.celrep.2021.110279 |
Citation | Engels R, et al. (2022) LFA1 and ICAM1 are critical for fusion and spread of murine leukemia virus in vivo. Cell Rep 38(3):110279 |
abstractText | Murine leukemia virus (MLV)-presenting cells form stable intercellular contacts with target cells during infection of lymphoid tissue, indicating a role of cell-cell contacts in retrovirus dissemination. Whether host cell adhesion proteins are required for retrovirus spread in vivo remains unknown. Here, we demonstrate that the lymphocyte-function-associated-antigen-1 (LFA1) and its ligand intercellular-adhesion-molecule-1 (ICAM1) are important for cell-contact-dependent transmission of MLV between leukocytes. Infection experiments in LFA1- and ICAM1-deficient mice demonstrate a defect in MLV spread within lymph nodes. Co-culture of primary leukocytes reveals a specific requirement for ICAM1 on donor cells and LFA1 on target cells for cell-contact-dependent spread through trans- and cis-infection. Importantly, adoptive transfer experiments combined with a newly established MLV-fusion assay confirm that the directed LFA1-ICAM1 interaction is important for retrovirus fusion and transmission in vivo. Taken together, our data provide insights on how retroviruses exploit host proteins and the biology of cell-cell interactions for dissemination. |