DOI: 10.1128/jvi.01936-06. Adenovirus Infection Triggers a Rapid, MyD88-Regulated Transcriptome Response Critical to Acute-Phase and Adaptive Immune Responses In Vivo

Adenovirus Infection Triggers a Rapid, MyD88-Regulated Transcriptome Response Critical to Acute-Phase and Adaptive Immune Responses In Vivo

10.1128/jvi.01936-06

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT Nearly 50 years ago, the discovery of interferon prompted the notion that host cells innately respond to viral invasion. Since that time, technological advances have allowed this response to be extensively characterized and dissected in vitro. However, these advances have only recently been applied to highly complex, in vivo biological systems. To this end, we exploited high-titer adenovirus (Ad) vectors to globally investigate the innate immune response to nonenveloped viral infection in vivo. Our results indicated a potent cellular transcriptome response shortly after infection, with global assessments revealing significant dysregulation in ∼15% of the measured transcripts derived from Ad vector-transduced tissue. Bioinformatics-based transcriptome analysis revealed a complex innate response to Ad infection, with induction of proinflammatory responses (and suppression of metabolism and mitochondrial genes) akin to those observed when mice are challenged with lipopolysaccharide. Despite this commonality, there were many unique aspects of the Ad-dependent transcriptome response, including the upregulation of several RNA regulatory mechanisms and apoptosis-related pathways, accompanied by the suppression of lysosomal and endocytic genes. Our results also implicated the Toll-like receptors (TLRs) in these responses, prompting specific investigations into this pathway. By using MyD88KO mice, our results confirmed that Ad-induced dysregulation of five functionally related gene clusters are significantly dependent on this TLR adaptor gene. MyD88 deficiency also resulted in significantly diminished, although not abolished, adaptive and acute-phase immune responses to Ad, confirming the transcriptome data, as well as specifically identifying MyD88 as a significant Ad immunity amplifier and regulator in vivo.

Bibliography

Hartman, Z. C., Kiang, A., Everett, R. S., Serra, D., Yang, X. Y., Clay, T. M., & Amalfitano, A. (2007). Adenovirus Infection Triggers a Rapid, MyD88-Regulated Transcriptome Response Critical to Acute-Phase and Adaptive Immune Responses In Vivo. Journal of Virology, 81(4), 1796â1812.

Authors 7

Zachary C. Hartman (first)
Anne Kiang (additional)
Ruth S. Everett (additional)
Delila Serra (additional)
Xiao Y. Yang (additional)
Timothy M. Clay (additional)
Andrea Amalfitano (additional)

References 46 Referenced 113

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Dates

Type	When
Created	18 years, 9 months ago (Nov. 22, 2006, 8:28 p.m.)
Deposited	3 years, 6 months ago (March 5, 2022, 6:29 a.m.)
Indexed	3 months ago (June 5, 2025, 12:50 a.m.)
Issued	18 years, 6 months ago (Feb. 15, 2007)
Published	18 years, 6 months ago (Feb. 15, 2007)
Published Print	18 years, 6 months ago (Feb. 15, 2007)

Funders 0

None

BibTeX

@article{Hartman_2007, title={Adenovirus Infection Triggers a Rapid, MyD88-Regulated Transcriptome Response Critical to Acute-Phase and Adaptive Immune Responses In Vivo}, volume={81}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.01936-06}, DOI={10.1128/jvi.01936-06}, number={4}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Hartman, Zachary C. and Kiang, Anne and Everett, Ruth S. and Serra, Delila and Yang, Xiao Y. and Clay, Timothy M. and Amalfitano, Andrea}, year={2007}, month=feb, pages={1796–1812} }

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