Impact of small, non-coding RNA expression on viral replication

• Applicant: Dr. Simone Backes
• Subject Area: Virology
• Term: from 2013 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 233526993

MicroRNAs (miRNAs), ~22 nucleotide small non-coding RNA molecules, play a crucial posttranscriptional regulatory role of gene expression in fundamental cellular processes. Several viruses profoundly impact the host miRNA profile or encode for their own miRNAs to manipulate both cellular and viral gene expression. There is substantial progress in understanding the biogenesis and functions of miRNAs encoded by nuclear double-stranded (ds) DNA viruses and the synthesis of engineered miRNA synthesis by cytoplasmic RNA viruses has been demonstrated. Poxviruses, a family of large cytoplasmic dsDNA viruses, have evolved a plethora of strategies to manipulate cellular pathways, but the expression of viral miRNAs or the interference with cellular miRNA has not been described. In addition, relatively little is known about the impact of host miRNAs on the pathogenesis of viruses. In poxvirus-infected cells, we have discovered that the viral Poly(A) polymerase VP55 induces global poly(A)-tailing of host miRNAs, resulting in a complete loss of their expression. Furthermore, small RNA profiling of infected cells uncovered a small, Dicer-dependent, poxvirus RNA that potentially represents a virus-encoded miRNA that surprisingly remains untailed.One aim of this study is to elucidate the biogenesis pathway of the poxvirus small RNA and determine its function as it relates to poxvirus infection. We also propose to use VP55 as a tool to expand our knowledge of the interplay between host miRNAs and the cellular response to infection. More specifically, we propose to engineer VP55-expressing viruses and inducible cell-lines to study the impact of host miRNAs on gene expression and replication of different viruses. The long-term goal of this study is the identification of new targets for antiviral therapy.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Benjamin TenOever, Ph.D.