Lymphocytic choriomeningitis arenavirus utilises intercellular connections for cell to cell spread

Area of Science:

• Virology
• Cell Biology
• Infectious Diseases

Background:

• Arenaviridae viruses, including Lassa and LCMV, cause severe hemorrhagic fevers and neurological diseases.
• Lymphocytic choriomeningitis arenavirus (LCMV) is a model arenavirus for studying viral biology and pathogenesis.
• Previous understanding suggested arenavirus spread primarily occurs via extracellular routes.

Purpose of the Study:

• To investigate alternative transmission routes for arenaviruses, specifically LCMV.
• To determine the role of intercellular connections in LCMV spread.
• To elucidate the mechanisms underlying arenavirus cell-to-cell transmission.

Main Methods:

• Utilized cultured cells infected with LCMV.
• Employed confocal and STED microscopy to visualize viral components within intercellular connections.
• Used LCMV-neutralizing antibodies to block extracellular spread and quantify intercellular transmission.

Main Results:

• Identified actin- and tubulin-rich, nanotube-like connections between LCMV-infected and uninfected cells.
• Observed LCMV virion components and genomic RNA within these intercellular connections.
• Demonstrated that approximately 50% of LCMV transmission occurs through these intercellular connections when extracellular spread is blocked.

Conclusions:

• Arenaviruses, including LCMV, utilize intercellular connections, resembling tunnelling nanotubes (TNTs), for transmission.
• Viral spread is more complex than previously assumed, involving both extracellular and direct cell-to-cell routes.
• Understanding these novel transmission pathways is crucial for developing effective antiviral strategies against arenavirus infections.