title: Suppression of transforming growth factor β receptor 2 and Smad5 is associated with high levels of microRNA miR-155 in the oral mucosa during chronic simian immunodeficiency virus infection.
abstract: Chronic human immunodeficiency virus and simian immunodeficiency virus (HIV and SIV) infections are characterized by mucosal inflammation in the presence of anti-inflammatory cytokines such as transforming growth factor β (TGFβ). The mechanisms for refractiveness to TGFβ are not clear. Here we show that the expression of microRNA miR-155 was significantly upregulated in the oropharyngeal mucosa during chronic SIV infection and was coincident with downregulation of TGFβ receptor 2 (TGFβ-R2) and SMAD5, key TGFβ signaling genes that harbor putative target sites for miR-155. Ectopic expression of miR-155 in vitro was found to significantly downregulate TGFβ-R2 and Smad5 expression, suggesting a role for miR-155 in the suppression of TGFβ-R2 and SMAD5 genes in vivo. The downregulation of TGFβ signaling genes by miR-155 likely contributes to the nonresponsiveness to TGFβ during SIV infection and may inadvertently aid in increased immune activation during HIV and SIV infections.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Jeffy
authors.initials: J
authors.lastname: George
authors.affiliation: Bioqual Inc., Rockville, Maryland, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.affiliation: University of Florida, Gainesville, Florida, USA.
authors.forename: Rolf
authors.initials: R
authors.lastname: Renne
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA joseph.mattapallil@usuhs.edu.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Mattapallil
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D008253:Macaca mulatta; D035683:MicroRNAs / Q000235:genetics*; D009061:Mouth Mucosa / Q000473:pathology*; D009960:Oropharynx / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D051902:Smad5 Protein / Q000096:biosynthesis*
chemical_list: D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D051902:Smad5 Protein