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Engels, Rebecca; Falk, Lisa; Albanese, Manuel; Keppler, Oliver T. und Sewald, Xaver (2022): LFA1 and ICAM1 are critical for fusion and spread of murine leukemia virus in vivo. In: Cell Reports, Bd. 38, Nr. 3, 110279 [PDF, 2MB]

Abstract

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.

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