Arenaviruses are the largest family of haemorrhagic fever causing viruses. Endemic to West Africa and South America, these neglected, diverse and emerging RNA viruses cause persistent, often asymptomatic infections in their natural rodent hosts, Mastomys natalensis, and jump the species barrier to humans, through direct contact with infected animals, rodent excreta or contaminated household items or food.
Infection results in illnesses ranging from mild flu-like syndromes to severe and highly fatal haemorrhagic zoonoses. The seasonal and frequent outbreaks of the most common arenavirus, Lassa, across West Africa can cause an estimated 300,000 cases annually with associated lethality rates as high as 50%, emphasising that these viruses should no longer be treated as causes of sporadic epidemics.
The immense impact of these outbreaks on human health 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.
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.
Our research and its impact
Virus entry is a key determinant of viral host range, cellular tropism and disease outcome, therefore, targeting this step of the arenavirus lifecycle could have significant impact on the control of viral infection. We are 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.
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. The One Virology team is developing proteomic methods will reveal novel co-factors that define pathogenicity differences and will elucidate the molecular details of key host–virus interactions; exploiting these interactions is key in the application of this research to the design of therapeutics.