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Published on: December 17, 2016
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.
Abstract:
The role of the virion shell in viral pathogenesis is relatively unknown yet the use of viral vectors in human gene transfer experiments requires an understanding of these interactions. In this study, we used DNA microarrays to identify genes modulated during pathogenic adenovirus or nonpathogenic adeno-associated virus infections. Responses to wt viruses, recombinant vectors, or empty virion particles were compared. Adeno-associated virus shells induced nearly the full complement of changes elicited by the intact virus. The cellular genes elicited a nonpathogenic response, with antiproliferative genes being induced as a cluster. In contrast, adenovirus and adenovirus empty capsid infection yielded a broader response and subset, respectively, including induction of immune and stress-response genes associated with pathogenic effects. Our studies show that the impact of the viral capsid on cellular gene expression, and potential host toxicity, must be considered independent of the vector genome for safe gene transfer in the clinic.
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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