InstructThe latest webinar in the Instruct-ERIC Structure Meets Function series this month includes speakers who have accessed cutting-edge structural biology services through Instruct. The webinar series offers an insight into the very cutting edge of structural biology research, utilising the latest techniques available through Instruct-ERIC facilities and centres.
On 18 November, the webinar will feature speakers who have utilised several aspects of Instruct's service offering. Liina Hannula of the University of Helsinki conducted an internship at STRUBI in Oxford, part of Instruct-UK. Their talk will outline their work on Rabies lyssavirus, as well as their experiences as an Instruct intern. The second speaker will be Joseph McGrail of Universidad Autónoma de Madrid, describing their recent paper on Monkeypox and access to University of Helsinki through Instruct and ISIDORe.
Moderator: Hanna Oksanen - University of Helsinki
Speaker: Liina Hannula - University of Helsinki
Title: Towards a structural understanding of lyssavirus receptor interactions
Abstract: Lyssaviruses, such as rabies virus, cause devastating disease with limited options for treatment. The exact molecular mechanisms of lyssavirus infection remain incompletely understood, however. Lyssaviruses bind their host cell receptors with surface glycoprotein G, and there is evidence that a specific linear motif in the G protein is responsible for attachment of rabies virus to acetylcholine receptors, potentially inducing behavioural modifications. It is unclear whether related lyssaviruses, which differ from rabies virus in their G protein sequence, could use this motif to bind acetylcholine receptors. The goal of this internship project, supported by the Instruct-ERIC internship program and conducted at the Division of Structural Biology, University of Oxford, was to create a streamlined method to investigate the interactions of lyssaviruses with acetylcholine receptors. To this end, recombinant proteins containing the motif of interest were generated from the G proteins of selected lyssaviruses, fused with tags to aid protein purification and analysis. Interaction of the fusion proteins with a recombinant acetylcholine receptor analogue was assessed using biolayer interferometry (BLI). Diffracting crystals were obtained for structural analysis through co-crystallization of the receptor ectodomain and the interacting peptide from rabies virus G protein.
Speaker: Joseph McGrail - Universidad Autónoma de Madrid
Title: Comparative Analysis and ISG15 Role in MPXV Infection
Abstract: The 2022–2024 global outbreak of monkeypox virus (MPXV) has reignited interest in understanding viral determinants of transmission and host–pathogen interactions. MPXV, a member of the Poxviridae family, produces distinct viral forms—intracellular mature viruses (MVs) and extracellular enveloped viruses (EVs)—that contribute respectively to local infection and systemic dissemination. Comparative analyses of representative strains from Clades I and II reveal that the 2022 outbreak Lineage B.1 MPXV displays a significantly slower replication cycle than earlier Clade II isolates, accompanied by distinct proteomic and phosphoproteomic profiles. Expanding on these findings, we demonstrate that the interferon-stimulated gene ISG15 acts as a host determinant of MPXV replication and immune evasion. ISG15 deficiency enhances viral replication and protein synthesis, while clade-specific variation modulates viral sensitivity to ISG15 restriction. Notably, the 2024 Democratic Republic of Congo Clade Ib strain exhibits reduced ISG15 susceptibility, reflecting evolutionary divergence in host antiviral adaptation. Together, these results identify molecular and host-specific factors influencing MPXV replication and transmission, highlighting both viral and host contributions to the enhanced human-to-human spread characteristic of the recent Clade IIb outbreak.
