AAV Exploits Subcellular Stress Associated with Inflammation, Endoplasmic Reticulum Expansion, and Misfolded Proteins in Models of Cystic Fibrosis
2011

AAV and Cystic Fibrosis: How Stress Affects Viral Infection

publication 10 minutes Evidence: high

Author Information

Author(s): Johnson Jarrod S., Gentzsch Martina, Zhang Liqun, Ribeiro Carla M. P., Kantor Boris, Kafri Tal, Pickles Raymond J., Samulski R. Jude

Primary Institution: University of North Carolina, Chapel Hill, North Carolina, United States of America

Hypothesis

Cells under subcellular stress due to inflammation or misfolded proteins are more susceptible to viral infection.

Conclusion

The study found that subcellular stress significantly increases susceptibility to AAV infection in cystic fibrosis models.

Supporting Evidence

  • AAV infection was significantly enhanced in stressed human airway epithelial cells.
  • Cells expressing misfolded ΔF508-CFTR showed an order of magnitude increase in AAV transduction efficiency.
  • Rescue of misfolded ΔF508-CFTR under low temperature conditions restored viral transduction efficiency.

Takeaway

When cells are stressed, like in cystic fibrosis, they can get sick more easily from viruses. This study shows that a virus called AAV can take advantage of that stress.

Methodology

The study used human airway epithelial cell cultures and various CFTR mutant models to assess AAV infection efficiency under different stress conditions.

Limitations

The study primarily focused on specific cell models and may not fully represent in vivo conditions.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.ppat.1002053

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