%0 Journal Article %1 10.1371/journal.pntd.0009004 %A Moreno, H %A Rastrojo, A %A Pryce, R %A Fedeli, C %A Zimmer, G %A Bowden, T A %A Gerold, G %A Kunz, S %D 2020 %I Public Library of Science %J PLoS Negl Trop Dis %K pietschmann %N 12 %P 1-33 %T A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover %U https://doi.org/10.1371/journal.pntd.0009004 %V 14 %X Author summary Mammarenaviruses include emergent pathogens responsible of severe disease in humans in zoonotic events. The ability to use the human Transferrin receptor 1 (hTfR1) strongly correlates with their pathogenicity in humans. We isolated a new infectious Tamiami virus strain (TAMV-FL) from host-seeking ticks, which, contrary to the previous rodent-derived reference strain, can use hTfR1 to enter human cells. Moreover, serial passaging of TAMV-FL in human immunocompetent cells selected for two substitutions in the viral envelope glycoprotein: N151K and D156N. These substitutions increase the ability to highjack hTfR1 and the binding capacity to heparan sulfate proteoglycans and cause delayed endosomal escape. Our findings provide insight into the acquisition of novel traits by currently circulating TAMV that increase its potential to trespass the inter-species barrier.