Lymphocytic choriomeningitis arenavirus utilises intercellular connections for cell to cell spread.

Autor: Byford O; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Shaw AB; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Tse HN; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Moon-Walker A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.; Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.; Program in Virology, Harvard Medical School, Boston, MA, 02115, USA.; Merck Research Laboratories, Merck & Co, Cambridge, MA, 02141, USA., Saphire EO; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA., Whelan SPJ; Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, MO, 63110, USA., Stacey M; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK., Hewson R; Virology and Pathogenesis Group, National Infection Service, Public Health England, Porton Down, SP4 0JG, UK., Fontana J; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK., Barr JN; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK. j.n.barr@leeds.ac.uk.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. j.n.barr@leeds.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Nov 22; Vol. 14 (1), pp. 28961. Date of Electronic Publication: 2024 Nov 22.
DOI: 10.1038/s41598-024-79397-w
Abstrakt: The Arenaviridae family of segmented RNA viruses contains nearly 70 species with several associated with fatal haemorrhagic fevers, including Lassa, Lujo and Junin viruses. Lymphocytic choriomeningitis arenavirus (LCMV) is associated with fatal neurologic disease in humans and additionally represents a tractable model for studying arenavirus biology. Within cultured cells, a high proportion of LCMV spread is between directly neighbouring cells, suggesting infectivity may pass through intercellular connections, bypassing the canonical extracellular route involving egress from the plasma membrane. Consistent with this, we visualized abundant actin- and tubulin-rich connections conjoining LCMV-infected and uninfected cells within cultures, resembling tunnelling nanotubes (TNTs). Within these TNT-like connections, confocal and STED microscopy identified puncta containing the major structural components of LCMV virions alongside genomic RNA, consistent with intercellular transit of assembled virions or ribonucleoprotein genome segments. Blocking the extracellular route of infection by adding potent LCMV neutralising antibody M28 to supernatants during infection revealed around 50% of LCMV transmission was via intercellular connections. These results show arenaviruses transmission is more complex than previously thought involving both extracellular and intercellular routes.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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