Honours Research Scholarship
Ms Amanda Choo and Professor Suresh Mahalingam
A one-year scholarship of $10,000 has been awarded to Ms Amanda Choo for a research project in viral immunology entitled An ex vivo human model to study viral-induced rheumatic disease. The project is being undertaken at the Centre for Biomedical, Molecular and Chemical Sciences (CBMCS) at the University of Canberra (UC) under the supervision of Professor Suresh Mahalingam, NHMRC Fellow, Associate Dean Research, Director CBMCS, and Head of Biomedical Sciences.
Ms Choo is exploring the basic mechanisms underlying acute and chronic arthritis triggered by viral infections.
The following information has been extracted from Ms Choo's application for funding:
Viral arthritis is joint inflammation caused by a virus. Symptoms of viral arthritis include joint pain, stiffness, and swelling. Many viruses are known to cause arthritis including rubella virus, HIV, hepatitis viruses, Varicella Zoster Virus (chicken pox), human parvovirus, mumps virus, and mosquito borne viruses (e.g. Ross River virus). Some vaccinations with attenuated viruses (eg MMR immunization, rubella vaccination) are also known to cause inflammation. The mechanisms of these diseases are poorly understood. It is believed that a combination of host and viral factors contribute to disease. Host factors include age, sex, genetic background, infection history, and immune response while viral factors include the mode of host entry, tissue tropism, replication, the ability to establish persistent or latent viral infections, and alterations of host antigens. The virus team at the University of Canberra has developed a novel human cell culture model to study arthritic disease caused by viral infections. The existence of this model provides an excellent opportunity to explore the basic mechanisms of infectious arthritis which should prove more reliable and lead to improved therapies.
There is a substantial gap in knowledge on how viruses cause arthritis. Preliminary data with human bone cells will lay the foundation for the new understanding of viral-induced arthritis. Knowledge of the presence and sites of persistent infection may provide valuable insights into the classical clinical symptoms of persistent joint pain following virus infection of humans. A good understanding of whether bone-derived soluble factors contribute to the development of musculoskeletal disease will be achieved. This aim will determine whether osteoblasts/osteoclasts are the major source of soluble factors during infection since this would provide a direct link for bone-derived factors in the development of severe arthritic disease. In summary, this research proposal will significantly enhance our understanding of the pathogenesis of virus-induced rheumatic disease and may ultimately lead to improved therapies against these diseases.
Ms Amanda Choo
Much research into inflammatory diseases currently involves mice and rats. However, the mechanisms underlying acute and chronic arthritis triggered by viral infections are poorly understood, largely due to the poor reliability of current animal models of disease. These models often involve the use of chemicals (eg double stranded RNA) or the injection of human viruses to establish infection and inflammation. This can cause pain, suffering and distress to the animals. Subsequent in-vitro experiments are also often performed on primary murine cells in the presence of sera generated from animal sources. Physiological and genetic differences between the murine and human species mean that results from murine or rat studies have had little impact in the understanding of human disease. Therefore, it is essential that these experiments be translated across to the human model.
This project involves the development and characterisation of an ex vivo human bone cell model to investigate mechanisms of viral-induced arthritis. This project will also incorporate the evaluation of serum-free media in the maintenance of primary human osteoblasts and osteoclasts. The use of RRV-gfp avoids the need for monoclonal or polyclonal antibodies (derived from animals) to detect infected cells. Osteoblasts were chosen for this study because these cells are responsible for bone formation and any disruption in their function could result in severe pathological consequences. These studies have the potential to define the pathway whereby viral interactions with the host immune system lead to the development of an immunopathologic inflammatory response.