Year: 2020
Type: article
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.
Source: PLoS neglected tropical diseases
Institutions: Centre Hospitalier Universitaire Vaudois, Consejo Superior de Investigaciones Científicas, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Centre for Human Genetics, University of Oxford, University of Bern, Institut für Virologie und Immunologie, University of Veterinary Medicine Hannover, Foundation, Center for Experimental and Clinical Infection Research, Umeå University
Language: English
Topic: Viral Infections and Vectors
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,350
Awards: Human Genetics and Disease Biology: Core Renewal for the Wellcome Trust Centre for Human Genetics, G1305823213, G3873106536, Viral Plasticity Underlying Tropism And Pathogenesis/ Innate Immune Evasion Of Emerging Viruses, Host cell invasion by Lassa virus, The Language of Zoonosis: Rationalising Receptor-Mediated Spillover of Viral Pathogens at a Molecular Level, G8690818240
OpenAlex ID: W3116567336