Arenaviruses are the largest family of haemorrhagic fever causing viruses. Endemic to West Africa and South America, arenaviral haemorrhagic fevers, such as Lassa fever (LF), are on the priority list of the World Health Organisation (WHO) as diseases requiring urgent research and development measures. Human transmission of these RNA viruses occurs through direct skin contact with infected rodent faeces or urine, ingestion of contaminated food, or through respiratory exposure to rodent excreta, resulting in illnesses ranging from mild flu-like syndromes to severe and highly fatal haemorrhagic diseases. Recent increased frequency of outbreaks in Nigeria of Lassa virus (LASV) has emphasised that these viruses should no longer be treated as causes of sporadic epidemics. The immense public health and socio-economic impact of these outbreaks in Nigeria and other endemic countries is further exacerbated by the lack of vaccines and effective treatments. In addition, new strains of arenaviruses are being discovered, hence, virus sequence diversity is expanding and the likelihood of new outbreaks is increasing, for which disease severity and treatment options are unknown.
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 and Control Irrua Specialist Teaching Hospital (ISTH), Nigeria), Dr Deborah Ehichioya (Ambrose Alli University (AAU), Nigeria), Professor Janet Daly (University of Nottingham)