Herrero Group

Supervisors: Assoc Prof Lara Herrero, Prof Mark von Itzstein

Virology, Immunology, Cellular & Molecular Biology

Mosquito-transmitted viruses (arboviruses) cause a range of clinical manifestations including encephalitis, arthritis, arthralgia and myalgia. Viruses in this group include the arthritogenic chikungunya virus (CHIKV), Ross River virus (RRV) and the deadly Japanese Encephalitis virus (JEV). With climate change and increasing globalisation, emerging arboviruses such as JEV, CHIKV and RRV are all examples of viruses which could follow Zika and be the next pandemic. Combatting mosquito-borne diseases is one of our most pressing global health challenges.  We recently demonstrated that viral-induced disease is largely driven by activation of the host innate inflammatory response. We now aim to define the mechanisms underlying this inflammatory-mediated pathology. This project (backed by a prestigious NHMRC Synergy grant) will identify new host targets for the rapid development of innovative therapies against arboviruses of pandemic potential.

Techniques: mouse model of viral disease, clinical disease and joint hypersensitivity measurement, ELISA, real-time PCR, viral plaque assays, flow cytometry, histopathology, western blotting, immunohistochemistry.

Supervisors: Dr Lara Herrero, Dr Penny Rudd & Assoc Prof Thomas Morrison (University of Colorado, Denver, USA)

Virology, Immunology, Cellular & Molecular Biology

Alphaviruses are a group of arboviruses which cause a range of clinical manifestations including encephalitis, arthritis, arthralgia and myalgia. Viruses in this group include the arthritogenic chikungunya virus (CHIKV) and Ross River virus (RRV). CHIKV was originally confined to the African continent but since 2004 has rapidly expanded its global range and is now considered a re-emerging virus of global public health concern. RRV was originally considered endemic however in 2015 a large outbreak occurred in Queensland and Northern New South Wales. Recently, Victoria faced what will be the second Australian RRV outbreak in two years, sparking concern that the virus has changed its pattern of circulation and causing significant public concern. New evidence suggests that RRV has potential for emergence into new areas of the world in a similar pattern to CHIKV. While the mortality rates associated with alphaviral diseases remain low at >1 per 5,000 cases, the significant economic burden due extensive morbidity remains high. Combatting mosquito-borne diseases is one of our most pressing global health challenges.  We recently demonstrated that alphavirus-induced disease is largely driven by activation of the host innate inflammatory response, in particular the complement system. We now aim to define the mechanisms underlying complement-mediated pathology in alphaviral disease. We hypothesise that (i) Specific glycans expressed on alphaviral surface glycoproteins promote complement-mediated activation thereby driving the pathology of alphaviral disease, and (ii) interactions between alphaviral glycans and other (yet to be identified) host lectins also impact alphaviral disease.

Techniques: mouse model of viral arthritis, clinical disease and joint hypersensitivity measurement, ELISA, real-time PCR, viral plaque assays, flow cytometry, histopathology, western blotting, immunohistochemistry.

Supervisors: Dr Penny Rudd, Dr Lara Herrero & Prof Travis Klein (QUT)

Virology, Immunology, Cell Biology

Arthropod-borne arthritogenic alphaviruses such as chikungunya virus (CHIKV) and Ross River virus (RRV) cause large epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution emerging in new regions of the world. The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration leaving patients bed-ridden and incapacitated. Interactions between virus and host determine the course of infection and are likely to be critical in understanding viral pathogenesis and control. Alphaviruses display N-linked glycosylated transmembrane glycoproteins with the exact composition of the glycosylation being dependent on the host species and cell type in which the virion was assembled. Our aim is to use glycan and lectin array technologies to discover interactions between virus and human cells to inform the rational design of therapeutics. The identification of the protein glycosylation status and glycan binding specificities of alphaviruses and human cells of the joints (chondrocytes, bone, fibroblasts, muscles) will provide an understanding of the virus-human host cell interaction and, consequently, potential novel insights into pathobiology.

Techniques: Handling of primary human bone/chondrocyte/joint cells, viral plaque assays, flow cytometry. Experiments will be undertaking in the state-of-the-art glycobioanalytical facility that has equipment to support array printing and analysis.

Supervisors: A/Prof Lara Herrero, Dr Penny Rudd, Dr Arun Everest-Dass, external supervisors in Australia-wide state health departments

Virology, Viral-ecology, Cell Biology, Molecular Biology

The incidence of human and animal diseases caused by mosquito-borne pathogens has increased at an alarming rate globally. In nature, arboviruses are maintained in continuous transmission cycles between mosquito vectors and susceptible vertebrate hosts. The early interactions between the arbovirus and initially infected mosquitoes is likely to be a crucial step in determining whether the virus is able to successfully establish infection.

Understanding how viruses infect these cells will significantly expand our knowledge of how arboviruses are transmitted and cause disease. This project utilises glyco-analytical approaches, unique mosquito cells and an arbovirus model system to identify new markers associated with virus transmission by mosquitoes. Markers associated with transmission will be identified by establishing global glycome and lectin profiles of the cells derived from a major mosquito species. The overall objective of this proposal is to explore the glycomics of mosquito cells and its role in arbovirus mosquito infection.

Techniques: Handling of primary mosquito cells, cell culture, viral plaque assays, flow cytometry, molecular biology, glyco-analytical techniques using mass spectrometry and liquid chromatography. Experiments will be undertaking in the state-of-the-art glycobioanalytical facility.

Supervisors: Dr Penny Rudd & Dr Lara Herrero

Virology, Virus-Host Interactions, Therapeutic Treatments

Ross River (RRV) and chikungunya (CHIKV) viruses are mosquito-borne viruses that cause severe joint and muscle pain in humans, which can last months or even years and may become a cause of chronic pain and disability. CHIKV and RRV can be found in over 100 countries across the globe. In 2015, over 700 000 cases of chikungunya were reported in the Americas alone to the Pan American Health Organization (PAHO) regional office and that same year, Queensland saw the largest epidemic of RRV in 20 years with over 4000 cases in the first quarter.

There are currently no specific treatments for these alphaviruses. Pain relief is prescribed to help alleviate symptoms. This project focuses on examining the repurposing of currently available drugs towards the treatment of viral induced arthritides. Discovering new uses for approved drugs provides the quickest possible transition from bench to bedside and may lead to novel treatments, which could prove beneficial towards pain management for hundreds of thousands of arthritic patients worldwide.

Towards this, we will 1) Examine if the drugs reduce joint swelling and ameliorate overall disease outcomes in RRV/CHIKV infected mice 2) Characterise the inflammatory cytokine/chemokine patterns during and after drug treatment and 3) Identify novel biomarkers which may serve as clinical markers for disease monitoring and outcomes.

The resolution of this project may lead to significant advancements for the identification of novel treatment strategies for patients suffering from CHIKV and RRV.

Techniques: mouse models of CHIKV and RRV infection, clinical disease monitoring, in-vitro assays, real-time PCR, cell-culture, viral plaque assays, immuno- histochemistry, bioplex assays.

Supervisors: Dr Penny Rudd & Dr Lara Herrero

Virology, Virus-Host Interactions, Therapeutic Treatments

Alphaviruses are a global health threat to humans and animals alike causing severe disease ranging from lethal encephalitis to debilitating long-lasting arthritis. Classically, the Old World alphaviruses like chikungunya (CHIKV) are primarily associated with painful and chronic arthritis. Yet, in recent years, neurological sequela has been consistently associated with CHIKV infection. Several thousand neuro-virulence cases have been reported especially in the young and elderly.

Very few studies have been undertaken to determine the mechanisms involved in CHIKV neuropathogenesis. We want to answer fundamental questions about the mechanisms involved in CHIKV neurovirulence using a combination of in vitro, in vivo and ex vivo approaches. Towards this, we will look at 1) How CHIKV enters CNS cells and disseminates throughout the brain structures 2) Determine which immune responses are elicited after CHIKV infects brain cells and 3) Assess how inadequate immune responses contribute to CHIKV neuropathologies.

Since there is no current treatment or vaccine, basic knowledge gained about CHIKV-host interactions will play a pivotal role in the discovery of new treatment strategies. These therapies will aim to reduce or circumvent neurological complications involved in CHIKV central nervous system (CNS) disease by preventing viral entry and spread or by counter-acting immune mediated pathology.

Techniques: mouse model of CHIKV infection, clinical disease monitoring, in-vitro assays, real-time PCR, cell-culture, viral plaque assays, immunohistochemistry, confocal microscopy.

Supervisors: Dr Penny Rudd & Dr Lara Herrero

Virology, Epidemiology, Public Health

Ross River virus (RRV) is a serious disease with no specific treatment or vaccine. It affects thousands of Australians annually, in Queensland with an influenza-like disease and severe debilitating joint pain. It is the most common mosquito-borne virus on our shores. The virus is a burden to Australia and surrounding islands in the South Pacific including Papua New Guinea and Fiji, putting a great number of people in hospital each year.

Most medically important arboviruses are transmitted to humans from other vertebrate species. To be an important reservoir for human infection, the reservoir host must be attractive for arthropod vectors i.e. they must be able to feed on these hosts. The hosts must also develop viraemia that is high enough to allow transmission to susceptible blood-feeding vectors. The ideal hosts must equally have low mortality to the infection and there must be low herd immunity.

Serological studies and laboratory investigations have indicated that several domestic and wild animals serve as RRV reservoirs, including dogs, cats, possums, and horses. However, the primary reservoir hosts for RRV are marsupials with macropods playing a significant role.

In a recent publication, there is evidence for endemic circulation of Ross River virus in the Pacific Islands and the potential for emergence. This project aims at looking into what these potential reservoirs could be. Towards this we will 1) Examine susceptibility of various cell lines to RRV infection 2) Determine if Australian animals have antibodies against RRV 3) Assess if the target reservoirs identified and present in Samoa also have antibodies against RRV.

This project will have important ecological, clinical and public health outcomes. It will allow us to better understand disease ecology of RRV and help identify potential outbreaks and reduce the risk global spread.

Techniques: cell culture, in-vitro assays, real-time PCR, viral plaque assays, ELISA.

Supervisors: Dr Lara Herrero, Dr Penny Rudd & Prof Brendan Mackey (School of Environment & Sciences)

Bioinformatics, Virology, Modelling

Mosquitoes are considered the most important transmitters of disease globally. The diseases they transmit threaten more than half the world’s human population and are reported to have significant health impacts on many domestic species. The ecology of mosquitoes and their capacity to transmit pathogens is complex, involving both intrinsic factors such as virus susceptibility and extrinsic factors such as the effect of environmental pressures. Utilising experimental, statistical and simulation models we will investigate how future climate and land use change affects the spread and infectivity of key mosquito transmitted viruses, and apply scenario based risk assessments to analyse and map modelled risk factors and projected risks.

Techniques: Computer modelling, data mining, Bayesian modelling, bioinformatics

Supervisors: Assoc Prof Lara Herrero, Dr Penny Rudd, Prof Linfa Wang (Duke NUS), Dr Michelle Baker (CSIRO)

Virology, Epidemiology, Cell Biology, Glycobiology, Public Health

Zoonotic pathogens pose major threats including catastrophic social and economic impacts. Zoonotic infections are triggered by the ability of a pathogen to cross from animal to human. Bats have been shown to carry more than 200 viruses and a significant proportion of these viruses are zoonotic however very little is known about what makes bats unique hosts. This project aims to investigate the mechanisms of viral host interactions focusing on viruses of pandemic potential. Utilising innovative glycobiological technologies this research seeks to be the first ever to identify the “natural” glycome of the bat leading to better prediction and understanding of why bats are uniquely susceptibility to a multitude of important zoonotic viruses. This will fill a significant gap in our knowledge of bat physiology and the unique nature of bats in harbouring viral infections.

Techniques: Handling of primary bat cells, cell culture, viral plaque assays, flow cytometry, molecular biology, glyco-analytical techniques using mass spectrometry and liquid chromatography. Experiments will be undertaking in the state-of-the-art glycobioanalytical facility.