Viral Infectious Diseases

2022 HIGHLIGHTS

Responding to the Japanese encephalitis virus outbreak

In March, the analysis of a patient’s sample by the Royal Melbourne Hospital’s Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute led to the detection of the first ever case of Japanese encephalitis virus (JEV) in South Australia. Genome sequencing revealed the virus had a new genetic makeup never seen in Australia. Historically, JEV was limited to the Northern Territory, Queensland and parts of Western Australia in tropical regions. Yet, JEV cases emerged in new areas including in New South Wales, Queensland, South Australia and Victoria in 2022, totalling 37 cases compared to 15 in the past decade. Our team played a key role in the outbreak response. VIDRL led several surveillance programs funded by the Victorian Government and analysed more than 1000 samples for JEV exposure. VIDRL also established a Commonwealth Government-funded program to strengthen JEV testing and diagnostic capacity around the country to future-proof Australia against flavivirus outbreaks. The program runs until June 2024. 

Circadian rhythm influences HIV activity in people on antiretroviral therapy 

Researchers in the Lewin group discovered the activity of the human immunodeficiency virus (HIV) in individuals on antiretroviral therapy (ART) follows a daily pattern, known as a circadian rhythm. By collecting blood samples over a 24-hour period from males living with HIV, the team found that levels of HIV inside cells follow a predictable pattern throughout the day, similar to many genes and hormones and indeed our own sleep. Additionally, the study revealed a connection between the hormone estradiol, one of the main forms of estrogen, and the changes in the virus' activity. These discoveries have important implications for strategies aimed at curing HIV through activation of latent virus and clinical trial design for people living with HIV. Incorporating the time of HIV activity fluctuations, in the design of clinical trials for cure interventions will be important.

Genetic similarities support continued efficacy of VACV-based vaccines against new mpox strain

Just weeks after the emergence of MPXV-2022 (the new virus strain observed in the global mpox outbreak in 2022), virologists, co-led by University of Melbourne Professor Matthew McKay, a Laboratory Head at the Doherty Institute and Faculty of Engineering and Information Technology, evaluated the genetic similarities and differences between the vaccinia virus (VACV) and MPXV-2022 to assess whether the recommended VACV-based vaccine would work against the new variant. Using genomic and epidemiological data, they found that, despite minor differences between the two viruses, the immune system primed by VACV-based vaccination could effectively recognise both viruses, suggesting continued efficacy of VACV-based vaccines against this new variant of mpox.  

Molecular virology research uncovers nanobodies’ superpower against SARS-CoV-2

In a study led by University of Melbourne Dr Nicholas Gherardin, Postdoctoral Fellow at the Doherty Institute, researchers developed a series of nanobodies engineered to lock onto a crucial part of SARS-CoV-2 known as the receptor-binding domain (RBD). Often referred to as "miniature antibodies”, nanobodies are tiny antibody fragments with a remarkable ability to target specific molecules. By combining two different nanobodies on the same viral segment, the team observed an exponential surge in the neutralising power of each nanobody. This fascinating phenomenon seems to stem from these nanobodies acting as a molecular bridge, linking various spike proteins of the virus together. This discovery demonstrates the significant potential of nanobodies as a promising therapeutic pathway in dealing with respiratory viruses, such as SARS-CoV-2. 

The impact of mRNA innovations on advances in virology

A collaborative team of researchers from the Doherty Institute, Monash University and the University of Melbourne established Victoria’s first mRNA Innovation Hub, with support from the Victorian Government. The Hub aims to develop next-generation mRNA vaccines and therapeutics, while training cross-disciplinary mRNA scientists to drive innovation. Co-led by University of Melbourne Professor Damian Purcell, Virologist and Laboratory Head at the Doherty Institute, the Hub's Node based at the Doherty Institute leverages over three decades of experience in RNA research. The Node brings together expertise in high containment, in vitro cultivation (SARS-CoV-2, influenza, other viruses), animal infection models, analysis of viral RNA elements, testing of antiviral efficacy and assessment of immune responses. The Hub will enable end-to-end development of new mRNA vaccines and therapeutics targeting infectious and rare diseases. 

Earlier in 2022, the Institute secured an important agreement with Moderna to expedite vaccine development for infectious diseases. Researchers will provide genetic sequence data from pathogens that will be formulated into mRNA vaccines by Moderna and returned to the Institute to test in pre-clinical models. By harnessing cutting-edge mRNA technology, this collaboration holds the potential to revolutionise vaccine development timelines, rapidly addressing emerging infectious threats. The scope of this partnership spans infections such as HIV and tuberculosis, as well as neglected diseases like HTLV-1. 

Lab-grown nasal tissue enables accurate research on respiratory viruses 

A team of scientists, led by University of Melbourne Professor Elizabeth Vincan, a Laboratory Head at the Doherty Institute, successfully grew human nasal tissue in the lab, known as an “organoid”, to study respiratory viruses without the need for invasive collection of tissue samples. Organoids outperform conventional cell lines, offering a more accurate representation of virus-host interactions, potentially fast-tracking treatment development. In this study, the team infected the organoids with various SARS-CoV-2 variants. Remarkably, the Delta variant triggered substantial cellular damage, fusing cells together — a contrast to other strains, such as the Alpha strain that left cells unaffected. This achievement promises new insights into virus behaviour and therapeutic approaches. 

Tracking changes and prevalence of influenza viruses in Australia between 2020 and 2021

The WHO Collaborating Centre for Reference and Research on Influenza at the Doherty Institute is part of the global effort to monitor and respond to influenza. Over the years 2020 and 2021, they received and studied 2,393 samples of human influenza cases to understand the viruses' characteristics and how they respond to treatment. Some viruses were also grown to potentially use in vaccines. The team, led by the Royal Melbourne Hospital’s Professor Ian Barr, Deputy Director of the Centre, found that Influenza A viruses were more common than Influenza B viruses during that period. By testing the viruses against antiviral drugs, the team found that a few viruses received in 2020 were less responsive to treatment than others. This finding is key to tracking changes in the virus and to inform future decisions about vaccines and treatments. 

Avian influenza virus in Australia shows stark difference compared to its Northern Hemisphere counterpart 

A research project, led by University of Melbourne’s Dr Michelle Wille, Honorary Postdoctoral Researcher at the Doherty Institute, investigated Avian Influenza A virus (AIV) dynamics in the Southern Hemisphere, a region often overlooked in AIV research dominated by Northern Hemisphere studies. Researchers used genome sequencing to analyse the genetic makeup of 333 AIV samples collected from wild birds over 15 years. The findings unveiled Australia's role as a diverse AIV reservoir characterised by sporadic introductions and isolated circulation. Migratory shorebirds, rather than ducks, were most likely to host uncommon subtypes of the virus. Surprisingly, the analysis highlighted inconsistent virus movement patterns across Australia, which corresponded to unpredictable waterfowl distributions influenced by rainfall. The research demonstrates the distinctive AIV dynamics of the Southern Hemisphere compared to its northern counterpart, but also emphasises the critical significance of comprehending the animal-human interface for effective viral threat management. 

The collective, global impact of our virologists  

Virology experts at the Institute are leading global efforts to tackle viral infectious diseases through research collaboration, information sharing and advocacy for comprehensive strategies in response to pandemics and epidemics. 

In March, Nobel Laureates Professors Françoise Barré-Sinoussi and Peter Doherty, along with experts including Professor Sharon Lewin, Director of the Doherty Institute, and Professor Brendan Crabb, CEO of the Burnet Institute, shared insights into different pandemics and discussed global health readiness at a joint symposium by the Australian Institute for Infectious Disease (AIID) and Australian-French Association for Research and Innovation (AFRAN). The event underscored the collaborative infectious disease research between France and Australia and the significance of global health readiness. 

In May, the International Conference on Human Retrovirology united researchers, clinicians, and advocates, urging action against the widespread HTLV-1 epidemic. Similar to HIV, HTLV-1 can trigger chronic disease in some people, especially in Indigenous communities around the globe. Despite being discovered in 1980, advances in HTLV-1 have been limited. The global health community called for worldwide investment and public health strategies, aligning with effective approaches against viruses like HIV and SARS-CoV-2.

Ahead of World Hepatitis Day in 2022, world-leading experts, led by the Royal Melbourne Hospital’s Professor Peter Revill, Section Head, Molecular Virology Group at VIDRL at the Doherty Institute, published a roadmap in Nature Reviews Gastroentorology & Ehpatology to pave the way to a cure for people living with hepatitis B (HBV). The analysis suggested that the range of biological markers (biomarkers) used to track the disease should be expanded and that better monitoring should be established to measure the effectiveness of treatments. The roadmap is the first of its kind for HBV and identifies a path forward for academics, clinicians and industry to find better serum biomarkers to fast-track a cure.