A precision-cut lung slice platform for evaluating respiratory virus replication dynamics

Area of Science:

• Pulmonology
• Virology
• Pathology

Background:

• Studying respiratory viruses requires physiologically relevant and scalable experimental systems.
• Existing models like cell lines lack lung complexity, while animal models are costly and low-throughput.
• There is a need for improved experimental platforms to study respiratory virus infection mechanisms.

Purpose of the Study:

• To develop and validate a rapid and scalable precision-cut lung slice (PCLS) platform for respiratory virus research.
• To assess the utility of PCLS in modeling influenza A virus replication, pathology, and immune responses.
• To establish PCLS as a versatile tool for studying respiratory pathogens.

Main Methods:

• Developed a workflow for generating infection-ready precision-cut lung slices (PCLS) within 24 hours.
• Maintained tissue viability of PCLS over extended culture periods.
• Utilized influenza A virus to infect PCLS and analyze viral replication, pathology, and immune cell responses.

Main Results:

• The PCLS platform supports robust influenza A virus replication.
• PCLS recapitulated key infection-associated lung pathology.
• Localized immune cell responses within the respiratory epithelium were observed in infected PCLS.

Conclusions:

• Precision-cut lung slices (PCLS) offer a scalable and physiologically relevant model for respiratory virus research.
• PCLS overcome limitations of traditional cell lines and animal models.
• This platform is valuable for studying influenza virus and other respiratory pathogens.