MODULATION OF HUMAN CYTOMEGALOVIRUS REPLICATION BY MICRO-RNA 132 (miR132), MICRO-RNA 145 (miR145) AND MICRO-RNA 212 (miR212)

摘要

The present invention related to miR145, miR132, miR212, and the genes or gene products regulated by these miRNAs. miR145 is downregulated in cells infected with HCMV. This downregulation modulates expression of miR145 target genes, including IRS-1. Transfection of cells with a miR145 agent, such as a miR145 mimetic, reduces HCMV replication and protein expression. miR132 and miR212 are upregulated in cells infected with HCMV. This upregulation modulates expression of miR132 and miR212 target genes, including MeCP2 and RICS. Transfection of cells with a miR132 and/or a miR212 antagonist reduces HCMV replication and protein expression. Accordingly, the invention provides methods of attenuating HCMV replication by modulating, for example, miR145, miR132, and/or miR212, and targets thereof. Also provided are methods of detecting an HCMV infection, and compositions and kits useful for attenuating HCMV replication.

主权项

1. A method of inhibiting HCMV replication in a cell, comprising contacting the cell with an agent selected from the group consisting of:
(a) a miR145 agent in an amount effective to decrease the level of one or more miR145 targets; (b) an RNA silencing agent capable of mediating RNAi of one or more miR145 targets in an amount effective to decrease the level of one or more miR145 targets; (c) a miR132 antagonist in an amount effective to increase the level of one or more miR132 targets; (d) a miR212 antagonist in an amount effective to increase the level of one or more miR212 targets; (e) a miR132 target activating agent in an amount effective to increase the level of one or more miR132 targets; and (f) a miR212 target activating agent in an amount effective to increase the level of one or more miR212 targets,such that HCMV replication is inhibited.