Measles Virus Persistent Infection of Human Induced Pluripotent Stem Cells

Area of Science:

• Stem cell biology
• Virology
• Developmental biology

Background:

• Measles virus (MV) utilizes cellular receptors like signaling lymphocyte activation molecule (SLAM; CD150) and CD46 for infection.
• Expression patterns of these receptors during early embryonal differentiation stages in human-induced pluripotent stem cells (hiPSCs) are not well understood.
• hiPSCs offer a powerful model for studying early human development and disease.

Purpose of the Study:

• To investigate the susceptibility of hiPSCs to measles virus (MV) infection.
• To determine if MV infection affects the pluripotency and differentiation capacity of hiPSCs.
• To explore the potential of MV as a gene delivery vehicle in hiPSCs.

Main Methods:

• Establishment of two hiPSC lines (BGU-iPSCs and EMF-iPSCs) expressing CD46 and CD150.
• Infection of hiPSCs with MV and characterization of persistent infection.
• Assessment of hiPSC pluripotency and differentiation potential post-MV infection.
• Analysis of MV integration into the host cell genome.

Main Results:

• Both BGU-iPSCs and EMF-iPSCs were successfully infected by MV, forming persistent, noncytopathic cell lines releasing infectious virus.
• MV-infected hiPSCs retained their pluripotency and demonstrated in vitro differentiation into the three germ layers, including neuronal lineages.
• MV did not integrate into the hiPSC genome, indicating its potential as a non-integrating gene delivery vector.

Conclusions:

• hiPSCs are susceptible to MV infection, supporting persistent, noncytopathic viral replication.
• MV infection does not impair the pluripotency or differentiation potential of hiPSCs.
• MV represents a promising, non-integrating vector for gene delivery into hiPSCs, facilitating research into stem cell differentiation and gene function.