title: A mouse polyomavirus-encoded microRNA targets the cellular apoptosis pathway through Smad2 inhibition.
abstract: Some viruses and most eukaryotic cells have microRNAs that regulate the expression of many genes. Although many viral miRNAs have been identified, only a few have been included in in vivo functional studies. Here we show that a Py-encoded miRNA downregulates the expression of the pro-apoptotic factor Smad2, resulting in the suppression of the apoptosis pathway. To study the Py miRNA in an in vivo context, a miRNA-deficient mutant virus was created on the background of the LID virus strain which establishes a rapid and lethal infection in newborn mice. Apoptosis analysis on kidney tissues indicates that the pro-apoptotic pathway is targeted in the infected host as well. Suppression of apoptosis through targeting of Smad2 by the Py miRNA is expected to synergize with anti-apoptotic effects previously attributed to the polyoma tumor antigens in support of virus replication in the natural host.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Biological and Health Sciences, Texas A&M University-Kingsville, Kingsville, TX 78363, USA. Electronic address: chang.sung@tamuk.edu.
authors.forename: Chang Kyoo
authors.initials: CK
authors.lastname: Sung
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hyungshin
authors.initials: H
authors.lastname: Yim
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Andrews
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: thomas_benjamin@hms.harvard.edu.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Benjamin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000502:physiology* / Q000821:virology*; D016086:Lentivirus; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011120:Polyomavirus / Q000145:classification*; D034622:RNA Interference; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D051899:Smad2 Protein; C497783:Smad2 protein, mouse
keywords: Animal infection; Apoptosis; MicroRNA; Mouse polyomavirus; Smad2 a cellular target