Prof. Lee Gehrke

The research interests of the Gehrke laboratory center on understanding virus-host cell interactions that underlie diseases of humans and plants. The specific focus of the group is on positive strand RNA viruses, including dengue fever virus, West Nile virus, and alfalfa mosaic virus. All of the viral RNAs studied in the lab lack a poly(A) tail, thus distinguishing them from host cellular RNAs. A broad question that interests us is understanding why the absence of the poly(A) tail is an evolutionarily retained feature, and how these non-adenylated viral RNAs compete with the host mRNAs for the translational apparatus.

Upon entry, the host cell senses an invasion. Recent evidence suggests that structured viral RNAs can act as Pathogen Associated Molecular Patterns (PAMPs) that are recognized by host Pattern Recognition Receptors (PRR) to activate cell signaling. An immediate goal of the laboratory is to understand how specific viral RNA-protein interactions influence the viral life cycle and the host immune response. The triphosphate group found at the 5’ end of some viral RNA transcripts (5’ 3P) has been described recently as an important determinant of “self versus non-self” that allows cells to distinguish between viral and cellular RNAs. Our results suggest that the 5’ 3P cannot be the only determinant because some RNAs with a 5’ 3P are potent activators, while others cause no activation of innate immune signaling. We have identified a non-structured region in the hepatitis C virus (HCV) 3’ untranslated region RNA that activates innate immune signaling by interacting with the RNA helicase RIG-I. We hypothesize that RIG-I senses both the 5’ 3P and RNA sequence or structure, and current work is focused on understanding how RIG-I and other RNA helicases are activated to initiate an immune response.

Non-polyadenylated viral RNAs infect both animals and plants, and we seek to understand common cross-kingdom features of the translational apparatus that support expression of these structurally distinct templates. Although the mRNAs lack a poly(A) tail, biochemical and functional evidence suggests that poly(A) binding protein (PABP) is functional in translating both poly(A)+ and poly(A)- mRNAs. We are working to test a hypothesis stating that the lack of the poly(A) tail gives the virus a functional advantage(s) over the cellular RNAs. This might explain why the absence of the poly(A) tail has been maintained over evolution as a feature common to a large number of positive-strand RNA viruses. High throughput screening is being done to identify small molecules that differentially affect translation of polyadenylated and non-adenylated messenger RNAs.

We are an “RNA lab” and rotation work with our group would provide experience in viral RNA replication, RNA transcription and translation, RNA-protein interactions, signal transduction, cell culture, and RNA structure.