Pathogenetic Role of miRNAs in Herpesvirus Infection

Micro-RNAs (miRNAs) are small, non-coding RNAs of about 22 nucleotides size. They play important roles in gene-regulation and have effects on a plethora of biological processes like development, cell-differentiation and programmed cell death. Although exhibiting no catalytic activity, miRNAs cause a specific reduction of protein expression by guiding proteins of the Argonaute family to non-coding regions of a targeted messenger RNA (mRNA). The Argonaute proteins provoke a decay or translational halt of this mRNA and therefore constitute an additional regulation mechanism within the cell. Currently, little is known about the role of miRNAs in the pathogenesis of human diseases. Recently, it was shown that also some viruses and notably herpesviruses encode miRNAs, and that cellular miRNAs can influence virus replication. The eight currently known human herpesviruses cause a variety of different diseases ranging from self-limiting childhood diseases with rash to severe and life-threatening diseases, congenital and generalized infections as well as malignancies. This multidisciplinary research program, consisting of 7 subprojects, investigates the role of viral and cellular miRNAs in the pathogenesis of herpesvirus infections using different cutting-edge technologies and representative species from human herpesvirus subfamilies.

For several herpesvirus representatives, we focus on:

(i) the role of viral and cellular miRNAs in replication and pathogenesis (e.g. tumorigenesis, cell cycle control and apoptosis),

(ii) the spatial (tissue specificity) and temporal distribution of viral and cellular miRNAs during infection, and

(iii) the identification and the role of the viral and cellular components involved in these processes.

The identification of target structures will be pursued by complementary, parallel approaches using expression profiling (on mRNA de novo synthesis, abundance and decay), proteomics/mass spectrometry and RISC pull-down technologies. The outcome of this highly collaborative research program will be fundamental for this new area of research, the role of miRNAs in human diseases, and will possibly identify a novel class of therapeutical targets.

Latest results can be found in detail in the descriptions of the subprojects