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.
LFA1 and ICAM1 are critical for fusion and spread of murine leukemia virus in vivo / M. Engels, L. Falk, M. Albanese, O. Keppler, X. Sewald. - In: CELL REPORTS. - ISSN 2211-1247. - 38:3(2022), pp. 110279.1-110279.17. [10.1016/j.celrep.2021.110279]
LFA1 and ICAM1 are critical for fusion and spread of murine leukemia virus in vivo
M. Albanese;
2022
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.File | Dimensione | Formato | |
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