The in vivo cellular response to adenovirus and its regulation through MyD88

ABSTRACT: While recent studies of immunity have uncovered many aspects of the innate immune system, there has been precious little investigation of the cellular response to viruses in vivo. To this end, we exploited high titer adenoviral (Ad) vectors to investigate the cellular response to non-enveloped viral infection in vivo. Our results indicate a potent cellular transcriptome response early after infection, with global assessments revealing significant dysregulation in ~15% of measured transcripts derived from Ad infected tissue. Transcriptome analysis revealed a complex interplay between the innate and adaptive responses, with suppression of metabolism and mitochondrial genes akin to those observed when mice are challenged with LPS. But despite this common response profile, there were many unique aspects of the Ad dependent trancriptome response, including upregulation of several RNA regulatory mechanisms and apoptosis-related pathways, accompanied by suppression of lysosome, endocytic, Wnt, and Calcium signaling pathways. Investigations into the TLR pathway using MyD88KO mice revealed that Ad induction of the TLR, MAPK, and cytokine receptor genes are significantly dependent on MyD88, as well as five other functional gene modules (mitochondrial, RNA regulation, cell cycle and growth, extracellular, and immune response genes). Absence of MyD88 also resulted in a greatly diminished Th1 response and acute phase response at later time points, confirming the important role MyD88 plays as an anti-adenoviral immunity amplifier and regulator in vivo. However, continued activation of immune response genes in Ad infected MyD88KO mice indicates that MyD88 is not the only component of the Ad ‘sensing mechanism’ in vivo. Keywords: Infectious response, pathogen response

ORGANISM(S): Mus musculus

PROVIDER: GSE4339 | GEO | 2006/04/04

SECONDARY ACCESSION(S): PRJNA94769

REPOSITORIES: GEO