In Vivo Imaging of Oncolytic Measles Virus Propagation with Single-Cell Resolution

Area of Science:

• Oncology
• Virology
• Biotechnology

Background:

• Recombinant measles viruses (MVs) demonstrate oncolytic activity against various human cancers.
• The kinetics of MV spread within tumors remain largely unexplored, hindering therapeutic optimization.

Purpose of the Study:

• To investigate and compare the tumor cell infection and spread kinetics of fusogenic and hypofusogenic recombinant measles viruses (MVs).
• To understand the influence of viral fusogenicity and spatial cell relationships on oncolytic virus therapy outcomes.

Main Methods:

• Establishment of an intravital imaging system using the dorsal skin fold chamber for serial, non-invasive monitoring.
• Infection and replication analysis of both fusogenic and hypofusogenic MVs in tumor models.
• Quantification of infected cell kinetics, infection foci size, and syncytia formation.

Main Results:

• Hypofusogenic MV-infected cells were detected at 3 days post-infection (dpi), peaking at 6 dpi.
• Fusogenic MV replicated faster, with detectable infection at 1 dpi and rapid cell killing.
• Fusogenic MV resulted in significantly larger infection foci compared to hypofusogenic MV; both formed syncytia.

Conclusions:

• Viral fusogenicity significantly impacts the kinetics of tumor cell infection and spread by recombinant measles viruses.
• The spatial arrangement of tumor cells plays a crucial role in the efficacy of oncolytic virus therapy.
• Understanding these dynamics is essential for developing more effective measles virus-based cancer treatments.