A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover
| Autor: | Stefan Kunz, Hector Moreno, Rhys Pryce, Chiara Fedeli, Thomas A. Bowden, Alberto Rastrojo, Gisa Gerold, Gert Zimmer |
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| Přispěvatelé: | Swiss National Science Foundation, Université de Lausanne, Knut and Alice Wallenberg Foundation, TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany. |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology RC955-962 Infektionsmedicin Biochemistry Database and Informatics Methods Ticks Medical Conditions Viral Envelope Proteins Arctic medicine. Tropical medicine Zoonoses Immune Physiology 600 Technology Chlorocebus aethiops Medicine and Health Sciences Arenaviridae Pathogen Arenaviruses New World Immune System Proteins 3. Good health Chemistry Infectious Diseases Viral Envelope Physical Sciences 293T cells Receptors Virus Cell lines 590 Animals (Zoology) Public aspects of medicine RA1-1270 Biological cultures Sequence Analysis Research Article Infectious Medicine Substitution Mutation Viral Entry Bioinformatics 030106 microbiology Immunology Sequence alignment Transferrin receptor 610 Medicine & health Viral quasispecies Biology Transfection Microbiology Virus Antibodies Viral hemorrhagic fever Cell Line 03 medical and health sciences Chlorides Viral entry Antigens CD Virology Receptors Transferrin medicine Genetics Animals Arenaviridae Infections Humans Amino Acid Sequence Molecular Biology Techniques Vero Cells Molecular Biology HEK 293 cells Public Health Environmental and Occupational Health Chemical Compounds Biology and Life Sciences Proteins medicine.disease Insect Vectors Research and analysis methods 030104 developmental biology HEK293 Cells Mutation Sequence Alignment Viral Transmission and Infection |
| Zdroj: | Digital.CSIC: Repositorio Institucional del CSIC Consejo Superior de Investigaciones Científicas (CSIC) Moreno, Hector; Rastrojo, Alberto; Pryce, Rhys; Fedeli, Chiara; Zimmer, Gert; Bowden, Thomas A; Gerold, Gisa; Kunz, Stefan (2020). A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover. PLoS neglected tropical diseases, 14(12), e0009004. Public Library of Science 10.1371/journal.pntd.0009004 Digital.CSIC. Repositorio Institucional del CSIC instname PLoS Neglected Tropical Diseases e0009004 PLoS neglected tropical diseases United Kingdom United States PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0009004 (2020) |
| DOI: | 10.1371/journal.pntd.0009004 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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