Research statement

The Allen Laboratory is interested in understanding RNA virus infections and the features of these viruses that drive their highly dynamic epidemiology, allowing them to emerge and persist in human populations, as well as understanding virus-host interactions that influence the infection process and define clinical outcomes.

Our research is particularity focused on enteric virus infections – including norovirus, rotavirus, hepatitis E virus and enteroviruses – as well as emerging virus infections including Crimean-Congo Haemorrhagic Fever Virus (CCHFV).

RNA viruses are major causes of morbidity in infant and adult populations worldwide, and in specific populations can be a cause of severe disease, exacerbate existing conditions/co-morbidities, and lead to disability or death. There is extensive diversity among the viruses associated with such infections, which includes rapidly evolving RNA viruses of different families that are associated with genetic changes that lead to rapid global emergence events. These genetic changes can lead to antibody-escape variants that evade individual and population level immunity or can lead to changes in virus-encoded proteins that enhance antagonism of host antiviral responses by novel mechanisms.

The viral pathogens associated with non-bacterial diarrhoeal disease, non-malarial fever and influenza-like illness remain poorly understood, and their burden on health in low-to-middle economic settings is often unrecognised. Here, gaps in diagnostic methodologies or lack of availability of adequate (or any) diagnostics can lead to under-attribution of viral aetiologies, and the presumption of bacterial infection resulting in inappropriate use of antimicrobial therapy to treat viral infections, and thereby intensifying problems such as antimicrobial resistance.

More recently, studies have identified host factors that are associated with outcomes of virus infection, controlled or influenced by host restriction factors and antiviral pathways important in control of enteric and respiratory virus infections, which need to be more robustly understood. With these studies has come observations on the genetic variability across the human population for loci encoding these mechanisms, with genetic polymorphisms making some factors absent/more common in different population groups.

Research themes: Taken together, there is a clear need to:

  1. better understand the viruses associated with important illnesses with significant global burden of disease by enhancing syndromic diagnostic technology available in all economic settings and to improve attribution of illness to viral infections;
  2. refine the molecular epidemiology of these viral infections and understand how genetic variation in the virus genome leads to emergence of novel strains;
  3. explore and understand the mechanisms of emergence used by which viruses such as enhanced or altered pathogenicity, host range, tropism or innate/adaptive immune-avoidance;
  4. undertake population-based studies to understand how host genetics may influence susceptibility to, and outcomes of, infection.

Approaches: Technologies such as rapid and multiplexed molecular detection methods and laboratory and field technologies for pathogen-agnostic sequencing will be important in understanding points [1] and [2], and research tools such as metagenomics, virus reverse genetics, molecular virology, structural biology, serology, mutagenesis, virus isolation and culture and use of genetically engineered cell lines to address points [3] and [4].

Impact: Improving diagnostic methods and access to these will directly improve patient health and outcomes and is a worthwhile endeavour. However, integrating these studies with strain characterisation and mechanistic research into virus emergence and virus-host interactions will pave the way to novel control strategies, predictive global surveillance systems, new therapeutics and improved vaccines.