Host-pathogen interactions in Hantavirus infections: a focus on cytoskeleton Crosstalk

• Applicants: Professor Dr. Salvatore Chiantia; Dr. Roland Schwarzer
• Subject Area: Virology ; Biophysics ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 524028135

Hantaviruses are a family of emerging, zoonotic viruses that can cause life-threatening diseases in human with high case-fatality rates. No approved antivirals exist, nor are effective vaccines available so that measures to combat hantavirus diseases and evolving epidemics are limited to symptomatic treatment and exposure prevention. The genomic and structural organization of hantaviruses is well understood, important host-pathogen-interactions on the other hand remain elusive. In recent years, increasing evidence was gathered for a broad structural reorganization of infected cells, which eventually leads to the formation of specialized, virus-producing compartments, the so-called viral factories. However, the underlying molecular mechanisms and the causative interactions between viral and cellular proteins are hitherto unknown. With this project we seek to close this gap and characterize the intracellular interactions of the hantavirus structural proteins, Gc, Gn and N with key components of the cytoskeleton, namely actin, vimentin and microtubules. Our preliminary data and previous publications suggested that, N protein and, in particular the cytoplasmic tail of Gc are involved in these activities. Based on that we hypothesize that hantavirus proteins bind and remodel cytoskeletal structures, thus promoting virus proliferation and impairing cellular processes that rely on cytoskeleton integrity. Our goals in this study are fourfold: 1) We will first broadly explore and thoroughly characterize interactions of hantaviruses with cytoskeletal proteins. 2) We will then investigate the impact of cytoskeleton knockdowns on hantavirus infections and protein processing. 3) We are going to reveal the structural changes in the cytoskeleton that occur as a result of infection and investigate the impact on cellular functions such as mitosis, cell migration and fluid-phase uptake. 4) We will explore whether pharmacologic manipulation of the cytoskeleton can be used as a novel antiviral treatment. Our consortium consists of two groups with highly complementary expertise. Dr. Schwarzer and his group at the university hospital Essen have a strong background in virology and cell biology, whereas the laboratory of Prof. Dr. Chiantia is specialized on advanced, single molecule fluorescence microscopy methods. We believe that this unique combination of skills and techniques will allow us to provide an in-depth understanding of the complex interplay between hantavirus structural proteins and key components of the host cell cytoskeleton.

• DFG Programme: Research Grants
• International Connection: Chile, Slovakia
• Cooperation Partners: Dr. Boris Klempa; Professorin Dr.-Ing. Nicole Tischler, Ph.D.