Arenaviruses
Our research and its impact
The current lack of understanding of the molecular mechanisms of key host–virus interactions that potentiate disease pathogenesis or impede disease potential through evasion of host cellular immunity, hampers the development of novel therapeutic strategies for arenavirus infection.
Host-restriction of arenavirus infection
The interplay between host cell immunity and viral replication is a key determinant of disease outcome during arenavirus infection; with potent suppression of the innate immune pathways being a hallmark of LASV infection. Host restriction factors are components of the intrinsic anti-viral response, that act at crucial steps to potently inhibit viral entry, replication and exit from the host cell. We are currently investigating the mechanisms of host restriction of arenavirus entry that may inform novel strategies to design therapeutic agents that utilise the host cell antiviral immunity to block emerging arenaviruses.
Collaborators: Dr Thomas Strecker (University of Marburg, Germany), Dr John Barr (University of Leeds), Dr Luisa Ciano (University of Nottingham)
Quantitative proteomics- Molecular mechanism of arenavirus pathogenesis
Despite the high genetic similarity amongst arenavirus strains, disease can vary from asymptomatic to fatal implying that the interplay between the host immune response and viral replication is a major predictive factor for disease outcome. It remains to be discovered what drives the observed difference
in phenotypes and what mechanisms govern the disparate responses to the host innate immune defence. We are developing proteomic methods to reveal novel co-factors that define pathogenicity differences and will elucidate the molecular and structural details of key host–virus interactions; exploiting these interactions is key in the application of this research to the design of therapeutics.
Collaborators: Dr Thomas Strecker (University of Marburg, Germany), Professor Janet Daly (University of Nottingham), Dr Ivan Campeotto (Nottingham Trent University, University of Leicester)
Public Health and Well-being Outreach Programmes
We have partnered with Lassa virus epidemiologists and virologists, Professor Danny Asogun and Dr Deborah Ehichioya, at the Irrua Specialist Teaching Hospital (ISTH) and Ambrose Alli University (AAU) in Nigeria to link the biomedical investigation with social engagement and communication to tackle the spread of the highly fatal arenavirus, Lassa (LASV), in endemic regions in Nigeria. Professor Asogun's efforts pioneered the establishment of the molecular diagnostic laboratory at ISTH in 2008, serving as the first National Reference laboratory for viral haemorrhagic fevers in Nigeria, and he has made significant contributions to Lassa fever case management in Nigeria. Our shared interests focus on identifying and developing novel therapeutic strategies for Lassa fever infection and on improving the engagement and support offered to affected communities in Nigeria. In the long-term, this work influence measures taken to predict and control future epidemics and may be informative to policy makers for the WHO and Public Heath England (PHE) when making decisions on how to effectively manage and identify suitable resources during a potential outbreak.
Collaborators: Professor Danny Asogun (FWACP, Foundation Director, Institute of Lassa fever Research & Control Irrua Specialist Teaching Hospital (ISTH), Nigeria), Dr Deborah Ehichioya (Ambrose Alli University (AAU), Nigeria), Professor Janet Daly (University of Nottingham) Our experts
Key people
Group Members: Dr Toshana Foster (Lab lead), Dr Robert Stott-Marshall (Postdoctoral Associate), Finley Old (BBSRC DTP Postgraduate student)
Dr Toshana Foster joined the University of Nottingham as a Nottingham Research Fellow in April 2018. Toshana received her Wellcome Trust PhD from the University of Leeds in 2011, where she biochemically and structurally characterized hepatitis C virus proteins, specifically solving one of the first solution nuclear magnetic resonance (NMR) spectroscopy structures of the monomeric form of the viroporin p7 for the rational design of virus inhibitors (Foster et al. 2014, Hepatology). Her postdoctoral research with Prof Stuart Neil at King’s College London, initially investigated the various aspects of HIV-1 cell biology particularly working collaboratively to study how Vpu exploits the endosomal trafficking machinery to counteract the restriction factor, tetherin and how the SCFβTRCP interaction motifs within Vpu may contribute to antagonism of tetherin. Alongside this research, she led a study on the role of IFITM-mediated antiviral activity against HIV-1. Key findings and successes from this work have influenced her current avenue of research that focuses on the molecular and cellular biology of arenaviruses and structural characterisation of host-protein interactions.
Current and previous funding: University of Nottingham Research Fellowship, Wellcome Seed Award in Science, Royal Society Research Grant, University of Nottingham Internal GCRF grant, Interdisciplinary Centre for Analytical Science (UNICAS) Inter-disciplinary Sandpit Programme Funding, MRC New Investigator Research Grant (NIRG)
Dr Robert Stott-Marshall attained his PhD on ‘The role of autophagy in Semliki Forest virus infection’ from Leeds Beckett University following on from an MSc degree that focused on the ‘Molecular and Cellular Biology of Parasites and Disease Vectors’ at the Liverpool School of Tropical Medicine. He then moved on to University of California Davis (UCD) as a Postdoctoral Scholar where he studied the role of flavivirus viral RNA trafficking in host cell nuclei, using live-cell microscopy techniques in tandem with viral RNA epitope tagging to track viral RNA during infection. Robert joined the group in December 2019 on a Wellcome Trust ‘Seed Award in Science’ and is now working on the MRC NIRG, with a focus on host-restriction of arenavirus infection.
Finley Old, a BBSRC DTP Postgraduate student, joined the group in January 2022. Fin achieved his undergraduate and Masters degrees from the University of Nottingham. For his Masters research project, Finley worked with Professor Jonathan Ball and Dr Patrick McClure on a project entitled: Generation of Bovine Antibody Repertoires Using Next-Generation Sequencing Techniques and 5’ RACE to Identify Areas of High Conservation in Bovine Antibody Heavy Chain Variable Region for Improved Forward Primer Design. Finley’s project focusses on unravelling the arenavirus interactome.
The current lack of understanding of the molecular mechanisms of key host–virus interactions that potentiate disease pathogenesis or impede disease potential through evasion of host cellular immunity, hampers the development of novel therapeutic strategies for arenavirus infection.
Host-restriction of arenavirus infection
The interplay between host cell immunity and viral replication is a key determinant of disease outcome during arenavirus infection; with potent suppression of the innate immune pathways being a hallmark of LASV infection. Host restriction factors are components of the intrinsic anti-viral response, that act at crucial steps to potently inhibit viral entry, replication and exit from the host cell. We are currently investigating the mechanisms of host restriction of arenavirus entry that may inform novel strategies to design therapeutic agents that utilise the host cell antiviral immunity to block emerging arenaviruses.
Collaborators: Dr Thomas Strecker (University of Marburg, Germany), Dr John Barr (University of Leeds), Dr Luisa Ciano (University of Nottingham)
Quantitative proteomics- Molecular mechanism of arenavirus pathogenesis
Despite the high genetic similarity amongst arenavirus strains, disease can vary from asymptomatic to fatal implying that the interplay between the host immune response and viral replication is a major predictive factor for disease outcome. It remains to be discovered what drives the observed difference
in phenotypes and what mechanisms govern the disparate responses to the host innate immune defence. We are developing proteomic methods to reveal novel co-factors that define pathogenicity differences and will elucidate the molecular and structural details of key host–virus interactions; exploiting these interactions is key in the application of this research to the design of therapeutics.
Collaborators: Dr Thomas Strecker (University of Marburg, Germany), Professor Janet Daly (University of Nottingham), Dr Ivan Campeotto (Nottingham Trent University, University of Leicester)
Public Health and Well-being Outreach Programmes
We have partnered with Lassa virus epidemiologists and virologists, Professor Danny Asogun and Dr Deborah Ehichioya, at the Irrua Specialist Teaching Hospital (ISTH) and Ambrose Alli University (AAU) in Nigeria to link the biomedical investigation with social engagement and communication to tackle the spread of the highly fatal arenavirus, Lassa (LASV), in endemic regions in Nigeria. Professor Asogun's efforts pioneered the establishment of the molecular diagnostic laboratory at ISTH in 2008, serving as the first National Reference laboratory for viral haemorrhagic fevers in Nigeria, and he has made significant contributions to Lassa fever case management in Nigeria. Our shared interests focus on identifying and developing novel therapeutic strategies for Lassa fever infection and on improving the engagement and support offered to affected communities in Nigeria. In the long-term, this work influence measures taken to predict and control future epidemics and may be informative to policy makers for the WHO and Public Heath England (PHE) when making decisions on how to effectively manage and identify suitable resources during a potential outbreak.
Collaborators: Professor Danny Asogun (FWACP, Foundation Director, Institute of Lassa fever Research & Control Irrua Specialist Teaching Hospital (ISTH), Nigeria), Dr Deborah Ehichioya (Ambrose Alli University (AAU), Nigeria), Professor Janet Daly (University of Nottingham) Our experts
Key people
Group Members: Dr Toshana Foster (Lab lead), Dr Robert Stott-Marshall (Postdoctoral Associate), Finley Old (BBSRC DTP Postgraduate student)
Dr Toshana Foster joined the University of Nottingham as a Nottingham Research Fellow in April 2018. Toshana received her Wellcome Trust PhD from the University of Leeds in 2011, where she biochemically and structurally characterized hepatitis C virus proteins, specifically solving one of the first solution nuclear magnetic resonance (NMR) spectroscopy structures of the monomeric form of the viroporin p7 for the rational design of virus inhibitors (Foster et al. 2014, Hepatology). Her postdoctoral research with Prof Stuart Neil at King’s College London, initially investigated the various aspects of HIV-1 cell biology particularly working collaboratively to study how Vpu exploits the endosomal trafficking machinery to counteract the restriction factor, tetherin and how the SCFβTRCP interaction motifs within Vpu may contribute to antagonism of tetherin. Alongside this research, she led a study on the role of IFITM-mediated antiviral activity against HIV-1. Key findings and successes from this work have influenced her current avenue of research that focuses on the molecular and cellular biology of arenaviruses and structural characterisation of host-protein interactions.
Current and previous funding: University of Nottingham Research Fellowship, Wellcome Seed Award in Science, Royal Society Research Grant, University of Nottingham Internal GCRF grant, Interdisciplinary Centre for Analytical Science (UNICAS) Inter-disciplinary Sandpit Programme Funding, MRC New Investigator Research Grant (NIRG)
Dr Robert Stott-Marshall attained his PhD on ‘The role of autophagy in Semliki Forest virus infection’ from Leeds Beckett University following on from an MSc degree that focused on the ‘Molecular and Cellular Biology of Parasites and Disease Vectors’ at the Liverpool School of Tropical Medicine. He then moved on to University of California Davis (UCD) as a Postdoctoral Scholar where he studied the role of flavivirus viral RNA trafficking in host cell nuclei, using live-cell microscopy techniques in tandem with viral RNA epitope tagging to track viral RNA during infection. Robert joined the group in December 2019 on a Wellcome Trust ‘Seed Award in Science’ and is now working on the MRC NIRG, with a focus on host-restriction of arenavirus infection.
Finley Old, a BBSRC DTP Postgraduate student, joined the group in January 2022. Fin achieved his undergraduate and Masters degrees from the University of Nottingham. For his Masters research project, Finley worked with Professor Jonathan Ball and Dr Patrick McClure on a project entitled: Generation of Bovine Antibody Repertoires Using Next-Generation Sequencing Techniques and 5’ RACE to Identify Areas of High Conservation in Bovine Antibody Heavy Chain Variable Region for Improved Forward Primer Design. Finley’s project focusses on unravelling the arenavirus interactome.