Neuropathogenic murine leukemia virus TR1.3 induces selective syncytia formation of brain capillary endothelium

Area of Science:

• Virology
• Neuroscience
• Cell Biology

Background:

• Murine leukemia virus (MLV) TR1.3 causes brain capillary endothelial cell (BCEC) fusion, cerebral hemorrhage, and death in newborn mice.
• While MLV infects endothelial cells in various organs, syncytia formation is exclusively observed in BCEC.

Purpose of the Study:

• To investigate whether viral or cellular factors dictate the selective syncytia formation in BCEC.
• To compare MLV infection and fusion capabilities of capillary endothelial cells (CEC) from different organs in vitro.

Main Methods:

• In vitro assay of CEC from multiple organs for MLV infection and cell fusion.
• Quantification of MLV infection via MLV envelope expression and infectious virus production.
• Comparison of syncytia formation in BCEC versus other CEC types post-MLV exposure.

Main Results:

• All tested CEC types demonstrated equal susceptibility to MLV infection, confirmed by viral envelope expression and infectious virus production.
• MLV-induced syncytia were exclusively observed in TR1.3-infected BCEC cultures.
• In vitro findings correlated with in vivo observations of MLV neuropathology.

Conclusions:

• The selective fusion and subsequent pathology of BCEC by MLV are determined by intrinsic properties unique to BCEC.
• These findings highlight BCEC-specific factors responsible for MLV-induced neuropathology, independent of viral infectivity levels.