Abstract
Rotaviruses are recognized as the leading cause of severe dehydrating diarrhea in infants and young children worldwide. Preventive and therapeutic strategies are urgently needed to fight this pathogen. In tissue culture and in vivo, rotavirus induces structural and functional alterations in the host cell. In order to better understand the molecular mechanisms involved in the events after rotavirus infection, we identified host cellular genes whose mRNA levels changed after infection. For this analysis, we used microarrays containing more than 38,000 human cDNAs to study the transcriptional response of the human intestinal cell line Caco-2 to rotavirus infection. We found that 508 genes were differentially regulated >2-fold at 16 h after rotavirus infection, and only one gene was similarly regulated at 1 h postinfection. Of these transcriptional changes, 73% corresponded to the upregulation of genes, with the majority of them occurring late, at 12 or more hours postinfection. Some of the regulated genes were classified according to known biological function and included genes encoding integral membrane proteins, interferon-regulated genes, transcriptional and translational regulators, and calcium metabolism-related genes. A new picture of global transcriptional regulation in the infected cell is presented and families of genes which may be involved in viral pathogenesis are discussed.
Acknowledgments
M.A.C. and D.A.F. contributed equally to this study.
This work was supported by a VA Merit Review grant, by NIH grants AI21362 and DK38707, and by DDC grant DK56339. Mariela A. Cuadras was on academic leave absence from the Instituto de Biotecnologia/UNAM, Cuernavaca, Morelos, Mexico, and was supported by an NIH-funded Emerging and Reemerging Infectious Disease fellowship (ID43TW00923).
We especially thank P. Brown and colleagues for technical advice and discussion.
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