Role of viral vectors and virion shells in cellular gene expression.
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.
Stilwell
Jackie L
JL
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7352, USA.
Samulski
Richard Jude
RJ
D000256:Adenoviridae / Q000235:genetics; D002213:Capsid / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016195:G2 Phase; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008938:Mitosis; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014771:Virion / Q000235:genetics*; D014780:Viruses / Q000235:genetics*
D008164:Luminescent Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D012313:RNA; D004247:DNA