1. LFA1 and ICAM1 are critical for fusion and spread of murine leukemia virus in vivo
- Author
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Rebecca Engels, Lisa Falk, Manuel Albanese, Oliver T. Keppler, and Xaver Sewald
- Subjects
Leukemia Virus, Murine ,Mice, Inbred C57BL ,Mice ,Tumor Virus Infections ,Leukemia, Experimental ,Macrophages ,Host-Pathogen Interactions ,Animals ,Lymphocytes ,Intercellular Adhesion Molecule-1 ,General Biochemistry, Genetics and Molecular Biology ,Lymphocyte Function-Associated Antigen-1 ,Retroviridae Infections - 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.
- Published
- 2021