Reovirus-induced alteration in expression of apoptosis and DNA repair genes with potential roles in viral pathogenesis.
Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-kappaB and c-Jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. We used high-density oligonucleotide microarrays to analyze cellular transcriptional alterations in HEK293 cells after infection with reovirus strain T3A (i.e., apoptosis inducing) compared to infection with reovirus strain T1L (i.e., minimally apoptosis inducing) and uninfected cells. These strains also differ dramatically in their potential to induce apoptotic injury in hearts of infected mice in vivo-T3A is myocarditic, whereas T1L is not. Using high-throughput microarray analysis of over 12,000 genes, we identified differential expression of a defined subset of genes involved in apoptosis and DNA repair after reovirus infection. This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease.
DeBiasi
Roberta L
RL
Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Clarke
Penny
P
Meintzer
Suzanne
S
Jotte
Robert
R
Kleinschmidt-Demasters
B K
BK
Johnson
Gary L
GL
Tyler
Kenneth L
KL
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012087:Reoviridae / Q000502:physiology*; D015398:Signal Transduction
D017931:DNA Primers