Decoding Virus-Host Interface Dynamics Across the Herpes Simplex Virus Lifecycle

• Applicants: Dr.-Ing. Boris Bogdanow; Professorin Dr. Fan Liu
• Subject Area: Virology ; Biochemistry ; Structural Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576180008

Viral infection depends on the ability of viral proteins to engage host factors through protein-–protein interactions (PPIs) that are both specific and dynamically regulated. In complex herpesviruses such as Herpes Simplex Virus Type 1 (HSV-1), these interactions orchestrate a multi-stage infectious cycle, requiring tight temporal control.However, a comprehensive understanding of stage-specific PPIs in herpesviruses, including their structural basis and functional consequences, remains elusive. This is largely due to methodological limitations: the lack of tools to map PPIs in intact, infected cells in a time-resolved manner; insufficient structural resolution; and limited insight into how physical interactions translate into functional outcomes.We propose that HSV-1 reprograms host pathways via dynamic PPIs. To systematically dissect this mechanism, we will develop a mass spectrometry–based pipeline that combines UV-induced cross-linking with bio-orthogonal labeling, integrated with structural modeling approaches. Our goal is to establish a time- and stage-resolved map of virus-host PPIs across the HSV-1 infectious cycle, with a particular focus on early, previously inaccessible events.Structure–function relationships will be built through cross-link-guided modeling and detailed investigation of PPI interfaces. We will systematically dissect PPI modes, with a focus on intrinsically disordered regions (IDRs) that harbor contain linear motifs (SLiMs).These SLiMs play a critical role in mediating transient interactions with distinct host proteins or recruit post-translational modifications depending on the infection stage. We will develop novel algorithms for SLiM prediction and validate them in an infectious context. As a central case study, we will mechanistically dissect how the viral tegument protein UL47 regulates host proteostasis.By resolving the spatial and temporal architecture of virus-host interactions at molecular detail, this project will deliver mechanistic insight into how herpesviruses manipulate host cell biology. Importantly, the methodological framework is scalable and readily transferrable to other pathogens and questions in cell biology.

• DFG Programme: Research Grants