Role of viral vectors and virion shells in cellular gene expression

Jackie L Stilwell1, Richard Jude Samulski

  • 1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA.

Insights

Viral capsids significantly influence gene expression and host toxicity. Understanding capsid effects independent of the genome is crucial for safe gene therapy development using viral vectors.

Area of Science:

  • Virology
  • Molecular Biology
  • Gene Therapy

Background:

  • The role of viral shells (capsids) in disease is not well understood.
  • Viral vectors are used in gene therapy, necessitating knowledge of capsid-host interactions.

Purpose of the Study:

  • To investigate how viral capsids from pathogenic adenovirus and nonpathogenic adeno-associated virus affect cellular gene expression.
  • To compare the responses to intact viruses, recombinant vectors, and empty viral particles.

Main Methods:

  • Utilized DNA microarrays to identify gene expression changes during viral infections.
  • Compared cellular responses to wild-type viruses, engineered vectors, and empty capsids.

Main Results:

  • Adeno-associated virus capsids induced a nonpathogenic gene expression profile, including antiproliferative genes.
  • Adenovirus capsids triggered a broader response, with immune and stress-response genes linked to pathogenicity.
  • Empty capsids from both viruses elicited distinct gene expression patterns.

Conclusions:

  • Viral capsids independently impact cellular gene expression and can cause host toxicity.
  • Capsid-mediated effects must be assessed separately from the vector genome for safe clinical gene transfer.

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