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
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
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DOI：
10.1128/jvi.03248-14
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发表时间：
2015-03-01
影响因子：
5.4
通讯作者：
Mattapallil, Joseph J.
中科院分区：
文献类型：
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作者：
George, Jeffy;Lewis, Mark G.;Mattapallil, Joseph J.
慢性人类免疫缺陷病毒和猿猴免疫缺陷病毒（HIV和SIV）感染的特征在于在抗炎细胞因子如转化生长因子β（TGF β）存在下的粘膜炎症。对TGF β的活化机制尚不清楚。在此，我们发现，在慢性SIV感染期间，口咽粘膜中microRNA miR-155的表达显著上调，并且与TGF β受体2（TGF β-R2）和SMAD 5的下调一致，这些基因是关键的TGF β信号传导基因，具有miR-155的推定靶位点。发现miR-155在体外的异位表达显著下调TGF β-R2和Smad 5的表达，表明miR-155在体内抑制TGF β-R2和SMAD 5基因中的作用。miR-155下调TGF β信号基因可能导致SIV感染期间对TGF β无反应性，并可能无意中有助于HIV和SIV感染期间免疫激活的增加。
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 beta (TGF beta). The mechanisms for refractiveness to TGF beta 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 TGF beta receptor 2 (TGF beta-R2) and SMAD5, key TGF beta signaling genes that harbor putative target sites for miR-155. Ectopic expression of miR-155 in vitro was found to significantly downregulate TGF beta-R2 and Smad5 expression, suggesting a role for miR-155 in the suppression of TGF beta-R2 and SMAD5 genes in vivo. The downregulation of TGF beta signaling genes by miR-155 likely contributes to the nonresponsiveness to TGF beta during SIV infection and may inadvertently aid in increased immune activation during HIV and SIV infections.