Loading...
A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover.
Moreno, Hector Rastrojo, Alberto Pryce, Rhys Fedeli, Chiara Zimmer, Gert Bowden, Thomas A Gerold, Gisa Kunz, Stefan
Moreno, Hector
Rastrojo, Alberto
Pryce, Rhys
Fedeli, Chiara
Zimmer, Gert
Bowden, Thomas A
Gerold, Gisa
Kunz, Stefan
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2020-12-28
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 3.85 MB
Other Titles
Abstract
A 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.
Citation
PLoS Negl Trop Dis. 2020 Dec 28;14(12):e0009004. doi: 10.1371/journal.pntd.0009004.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
1935-2735
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International