The TAM receptors play a crucial role in the regulation of the host type interferon (IFN)-I response, which represents a major branch of innate antiviral immunity [42; 43; 44]. Conserved PS receptors of the TAM/TIM families can mediate cell entry of a wide range of enveloped viruses via \"apoptotic mimicry\" [45]. Apoptotic mimicry consists of the utilization of TAM and TIM cellular receptors to mediate viral particle binding to the cell surface through recognition of PS exposed in viral membrane. Despite not directly involving viral GP interaction, viral particle architecture, GP abundance, and lipid composition of viral particles are factors that can determine PS accessibility to participating cellular receptors. Many emergent viruses benefit from apoptotic mimicry during zoonotic events and adaptation to new hosts [36; 46; 47; 48; 49; 50; 51; 52; 53]. The TAM family member Axl is a receptor tyrosine kinase (RTK) expressed in many human cell types and utilized by LASV in vivo [54], contributing to its entry [36; 37]. However, due to the high affinity binding between available DG and LASV\({}_{\text{GP}}\), the relative contribution of Axl RTK to LASV entry critically depends on the extent of functional glycosylation of DG. In cells lacking the glycosylated DG form, LASV viral particles cannot bind DG, and Axl RTK is able to promote viral entry acting as a functional receptor and mediating virus binding and internalization [36; 37]. Moreover, Axl RTK signaling also promotes the LASV endocytic macropinocytosis-like pathway [36; 37]. In human microvascular endothelial cells that express Axl RTK in the context of an under-glycosylated DG form, the two receptors, Axl RTK and DG, seem to cooperate [37]. Human epithelial cells lining the respiratory and digestive tracts, which are likely to be initial targets during zoonotic LASV transmission, express Axl RTK in combination with functionally glycosylated DG. Several lines of evidence support a crucial role of functionally glycosylated DG in productive LASV entry into human epithelial cells [25; 27; 36; 55; 56]. However, the exact role of Axl RTK in this context is currently unclear. It is conceivable that in epithelial cells, long DG-linked matriglycan chains reach above the glyocalix and capture free virus. This would make attachment of the virion to the PS receptors less relevant, a notion that has been supported, at least in part, by previous antibody perturbation studies [27; 36; 37]. However, this working model does not rule out a functional contribution of Axl RTK to DG-mediated LASV entry at steps upon early attachment or to DG-independent entry. Cellular factors participating in LASV virion entry determine cell susceptibility and affect subsequent steps of viral attachment. Indeed, RTKs, which are well-known upstream regulatory factors of macropinocytosis, participate in entry of a range of viruses [57; 58; 50; 59; 45], and therefore could be important for LASV entry. The hepatocyte growth factor receptor (HGFR) is an RTK expressed in many cell types, including epithelial cells, neurons, hepatocytes, and hematopoietic cells [60], some of which are important targets of LASV in vivo [61]. Despite its main function as a receptor to hepatocyte mitogen [62], HGFR participates in the control of cell motility, angiogenesis, the immune response, cell differentiation, and anti-appoptosis [63]. Furthermore, HFGR is involved in macropinocytosis [64] and its inhibition with EMD1204063 (EMD), an inhibitor currently tested in clinical trials for treatment of solid tumors [65], resulted in an antiviral effect against LASV infection [27]. Since work with replication-competent LASV is restricted to BSL4 high-containment facilities, for the present study, we employed a recombinant LCMV expressing the envelope (GP) LASV\({}_{\text{GP}}\) (rLCMV/LASV\({}_{\text{GP}}\)) to investigate the molecular mechanisms underlying LASV entry.