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A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover.

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.

SUBMITTER: Moreno H

PROVIDER: S-EPMC7794035 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover.

Moreno Hector H Rastrojo Alberto A Pryce Rhys R Fedeli Chiara C Zimmer Gert G Bowden Thomas A TA Gerold Gisa G Kunz Stefan S

PLoS neglected tropical diseases 20201228 12

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 zo ...[more]

PMID: 33370288

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Project description:Rodents, a diverse, globally distributed and ecologically important order of mammals are nevertheless important reservoirs of known and novel zoonotic pathogens. Ongoing anthropogenic land use change is altering these species' abundance and distribution, which among zoonotic host species may increase the risk of zoonoses spillover events. A better understanding of the current distribution of rodent species is required to guide attempts to mitigate against potentially increased zoonotic disease hazard and risk. However, available species distribution and host-pathogen association datasets (e.g. IUCN, GBIF, CLOVER) are often taxonomically and spatially biased. Here, we synthesise data from West Africa from 127 rodent trapping studies, published between 1964-2022, as an additional source of information to characterise the range and presence of rodent species and identify the subgroup of species that are potential or known pathogen hosts. We identify that these rodent trapping studies, although biased towards human dominated landscapes across West Africa, can usefully complement current rodent species distribution datasets and we calculate the discrepancies between these datasets. For five regionally important zoonotic pathogens (Arenaviridae spp., Borrelia spp., Lassa mammarenavirus, Leptospira spp. and Toxoplasma gondii), we identify host-pathogen associations that have not been previously reported in host-association datasets. Finally, for these five pathogen groups, we find that the proportion of a rodent hosts range that have been sampled remains small with geographic clustering. A priority should be to sample rodent hosts across a greater geographic range to better characterise current and future risk of zoonotic spillover events. In the interim, studies of spatial pathogen risk informed by rodent distributions must incorporate a measure of the current sampling biases. The current synthesis of contextually rich rodent trapping data enriches available information from IUCN, GBIF and CLOVER which can support a more complete understanding of the hazard of zoonotic spillover events.

Dataset Information

A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover.

Publications

A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover.

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