Abstract
Adenovirus vectors are known to induce certain genes and impact innate response networks, but a broad understanding of this process and its mechanisms is currently lacking. For this reason, we chose to investigate and characterize Ad innate immunity using homogeneous, primary MEF cells replete with all the elements of the pathogen-sensing Toll-Like Receptor (TLR) pathway. By using an array-based approach to maximally define transcriptome changes induced upon Ad vector infection, we discovered that Ad infection induces a potent gene and transcription factor network response. This response is characterized by significant changes in the expression of genes involved in focal adhesion, tight junction, and RNA regulation, in addition to TLR pathway and other innate sensing genes. Further investigation using human A549 cells knocked down for various TLR pathway adaptors, revealed significant impacts on the Ad initiation of NF-kB and interferon responses, thus confirming TLR involvement in Ad-mediated immunity across diverse species.
Original language | English |
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Pages (from-to) | 357-372 |
Number of pages | 16 |
Journal | Virology |
Volume | 358 |
Issue number | 2 |
DOIs | |
State | Published - Feb 20 2007 |
Bibliographical note
Funding Information:We would like to thank Delila Serra and Jun-Ping Wei for technical support in virus preparation and EMSA technical expertise; Drs. Peter Haverty and Ulas Karaoz for logistical support and help with the ROVER and CARRIE analyses; as well Dr. Joseph Nevins and P. Yao at Duke University. AA and ZH were supported in part by a grant from the Children's Miracle Network (Durham, NC), AA was further supported by NIH grants (RO1DK-069884, P01 CA078673) and the Osteopathic Heritage Foundation. Appendix A
Funding
We would like to thank Delila Serra and Jun-Ping Wei for technical support in virus preparation and EMSA technical expertise; Drs. Peter Haverty and Ulas Karaoz for logistical support and help with the ROVER and CARRIE analyses; as well Dr. Joseph Nevins and P. Yao at Duke University. AA and ZH were supported in part by a grant from the Children's Miracle Network (Durham, NC), AA was further supported by NIH grants (RO1DK-069884, P01 CA078673) and the Osteopathic Heritage Foundation. Appendix A
Funders | Funder number |
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Children's Miracle Network Fund for Sithisarn | |
National Institutes of Health (NIH) | RO1DK-069884 |
National Childhood Cancer Registry – National Cancer Institute | P01CA078673 |
Osteopathic Heritage Foundation |
Keywords
- Ad
- Innate immune response
- Microarray
- Toll-like receptor
ASJC Scopus subject areas
- Virology