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dc.contributor.authorMoreno, Hector
dc.contributor.authorRastrojo, Alberto
dc.contributor.authorPryce, Rhys
dc.contributor.authorFedeli, Chiara
dc.contributor.authorZimmer, Gert
dc.contributor.authorBowden, Thomas A
dc.contributor.authorGerold, Gisa
dc.contributor.authorKunz, Stefan
dc.date.accessioned2021-04-08T14:00:34Z
dc.date.available2021-04-08T14:00:34Z
dc.date.issued2020-12-28
dc.identifier.citationPLoS Negl Trop Dis. 2020 Dec 28;14(12):e0009004. doi: 10.1371/journal.pntd.0009004.en_US
dc.identifier.pmid33370288
dc.identifier.doi10.1371/journal.pntd.0009004
dc.identifier.urihttp://hdl.handle.net/10033/622826
dc.description.abstractA detailed understanding of the mechanisms underlying the capacity of a virus to break the species barrier is crucial for pathogen surveillance and control. New World (NW) mammarenaviruses constitute a diverse group of rodent-borne pathogens that includes several causative agents of severe viral hemorrhagic fever in humans. The ability of the NW mammarenaviral attachment glycoprotein (GP) to utilize human transferrin receptor 1 (hTfR1) as a primary entry receptor plays a key role in dictating zoonotic potential. The recent isolation of Tacaribe and lymphocytic choriominingitis mammarenaviruses from host-seeking ticks provided evidence for the presence of mammarenaviruses in arthropods, which are established vectors for numerous other viral pathogens. Here, using next generation sequencing to search for other mammarenaviruses in ticks, we identified a novel replication-competent strain of the NW mammarenavirus Tamiami (TAMV-FL), which we found capable of utilizing hTfR1 to enter mammalian cells. During isolation through serial passaging in mammalian immunocompetent cells, the quasispecies of TAMV-FL acquired and enriched mutations leading to the amino acid changes N151K and D156N, within GP. Cell entry studies revealed that both substitutions, N151K and D156N, increased dependence of the virus on hTfR1 and binding to heparan sulfate proteoglycans. Moreover, we show that the substituted residues likely map to the sterically constrained trimeric axis of GP, and facilitate viral fusion at a lower pH, resulting in viral egress from later endosomal compartments. In summary, we identify and characterize a naturally occurring TAMV strain (TAMV-FL) within ticks that is able to utilize hTfR1. The TAMV-FL significantly diverged from previous TAMV isolates, demonstrating that TAMV quasispecies exhibit striking genetic plasticity that may facilitate zoonotic spillover and rapid adaptation to new hosts.en_US
dc.language.isoenen_US
dc.publisherPLOSen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleA novel circulating tamiami mammarenavirus shows potential for zoonotic spillover.en_US
dc.typeArticleen_US
dc.identifier.eissn1935-2735
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalPLoS neglected tropical diseasesen_US
dc.source.volume14
dc.source.issue12
dc.source.beginpagee0009004
dc.source.endpage
dc.source.journaltitlePLoS neglected tropical diseases
dc.source.countryUnited Kingdom
dc.source.countryUnited Kingdom
dc.source.countryUnited Kingdom
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International