Beyond macrophages: FIPV tropism includes T and B lymphocytes

Area of Science:

• Virology
• Immunology
• Pathogenesis

Background:

• Feline infectious peritonitis (FIP) is a fatal disease caused by feline infectious peritonitis virus (FIPV), a virulent feline coronavirus (FCoV).
• Current understanding suggests FIPV primarily infects monocytes/macrophages, but susceptible cell types and invasion mechanisms are not fully defined.

Purpose of the Study:

• To investigate the full range of immune cells susceptible to FIPV infection and viral replication.
• To elucidate FIPV pathogenesis and immune cell invasion mechanisms in naturally occurring FIP.

Main Methods:

• Single-cell RNA sequencing
• Multiplex immunofluorescence
• In situ hybridization
• Analysis of lymph node aspirates and tissues from cats with effusive FIP.

Main Results:

• FIPV RNA and nucleocapsid protein were detected in T and B lymphocytes and myeloid cells.
• Subgenomic viral RNA was found in T cells, indicating viral genomic replication within these cells.
• FIPV RNA-positive lymphocytes persisted after treatment cessation and clinical recovery.

Conclusions:

• FIPV infects multiple immune cell types beyond monocytes/macrophages, challenging existing pathogenesis models.
• The findings provide insights into coronavirus-driven immune dysregulation, viral persistence, and potential for relapse.
• Feline infectious peritonitis serves as a valuable animal model for studying coronavirus infections and chronic immunopathology.