In summary, our results demonstrate that GP1 residues R111, D123, Y122, and F226 are important for hTfR1 binding and cellentry of MACV (Figs. 2 and 3) . These results are in accordance with a recent study demonstrating that the central region of GTOV GP1 (residues 85-221) interacts with hTfR1 and that residues 159-221 are essential for this interaction [17] . These results are also in agreement with the recently published structure of MACV GP1 bound to hTfR1 [25] . MACV GP1 R111, which is not conserved in any of the other New World arenaviruses, is part of interaction motif 1 and makes prominent contacts with hTfR1 bII-2 strand, namely V210 (Fig. 1, top panel, and Fig. 4) . F226, unique to MACV (W in other New World arenaviruses), is part of interaction motif 3 and has a hydrophobic interaction with hTfR1 V210, as well as a van der Waals contact with hTfR1 I201 and L212 (Fig. 1, top panel, and Fig. 4 ). D123 and Y122 are part of interaction motif 4 and are conserved between MACV, JUNV, and SABV. D123 forms a hydrogen bond with hTfR1 K344, whereas Y122 forms one with hTfR1 E343 and in addition contacts hTfR1 residues A293, E294, and A340 (Fig. 1, top into HeLa cells (Fig. 3) . In accordance, this mutant bound efficiently to the cell surface of Vero cells (Fig. 2C ) yet was unable to immunoprecipitate hTfR1 (Fig. 2B) . These results suggest that Y122 might be important for binding hTfR1 but dispensable for binding simian TfR1, or that additional receptors/attachment factors are facilitating binding and entry of MACV into Vero cells. Whereas TfR1 residues E343, A293, and A340 are conserved among human and simian TfR1, glutamate 294 is an aspartate in simian TfR1 and the proximal asparagine 292 is a lysine.