How The Immune Response Can Affect Influenza Virus And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$333,964.00
Summary
A strong immune response is essential for protection against viral infections. However, in some circumstances a strong immune response against viruses can actually further aggravate disease. In addition, an anti-viral immune response can trigger asthma attacks in allergic individuals. This research thus seeks to understand and therefore mitigate the potentially detrimental role of inflammation in influenza virus infections and asthma.
Development Of National Protocols For The Detection Of Influenza A H5N1
Funder
National Health and Medical Research Council
Funding Amount
$248,229.00
Summary
This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patie ....This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patient specimens. Australian laboratories need authoritative guidelines as to optimal influenza tests, target genes and reagents. Development of a simple, potentially automated type specific test for influenza A H5N1 antibody such as enzyme immunoassay (EIA) is also desirable, as widely used tests cannot distinguish between infection with H5 or other influenza types. Reference methods such as haemagglutination inhibition (HAI) are cumbersome. In this project mock specimens for virus and antibody detection will be created using viral cell culture and infected chicken derived influenza A H5N1. This will be undertaken in physical containment level 4 (PC4) facilities in Australia's designated human and animal PC4 laboratories. This material will be used for (i) specimen panels to compare the performance of candidate laboratory tests (ii) positive control material in all tests undertaken and (iii) quality assurance exercises to ensure high standards of testing. Using these panels the group will assess influenza H5N1 RT-PCR, tests for detection of influenza proteins including immunofluorescence, and rapid point of care influenza A detection tests available in Australia. An EIA method currently used to detect influenza antibodies from different animal species will be refined to develop a simple test for type specific detection influenza A H5N1 antibodies, and subsequently evaluated using animal sera. A standard method for HAI reference serology for use in public health laboratories will also be recommended, and the best approaches to high throughput automated RT-PCR, and performing RT-PCR in the field on portable instrumentation will be explored. Recommendations for standard protocols for influenza A H5N1 will be developed and will submitted for review and endorsement by Commonwealth ministerial advisory committees.Read moreRead less
Novel Insights Into The Mechanisms Of How Chikungunya Virus Cause Disease In Humans
Funder
National Health and Medical Research Council
Funding Amount
$554,808.00
Summary
Many of the most dangerous and easily transmitted infectious agents are viruses. The emergence of chikungunya virus globally and the recognition of this pathogen in the aetiology of chronic diseases show the need for a better understanding of how the virus cause disease. The expected outcomes are a better understanding of human alphaviral diseases, with a view to improving prevention and treatment strategies to reduce the disease burden of CHIKV and related viruses.
Understanding And Modulating Hyperinflammation Caused By Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
In humans, highly pathogenic influenza A virus (IAV) infections can be fatal, as the disease is untreatable with available vaccine or anti-viral drugs. My fellowship aims to advance our knowledge of the mechanisms by which the immune system induces and regulates inflammation during IAV infection, which can be both helpful and detrimental in fighting the infection. This is critical for identifying and developing new therapies for severe IAV infections in the future.
The Role Of The Inflammasome In Modulating Disease During Influenza Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,979.00
Summary
Highly pathogenic influenza A virus (IAV) infections in humans are associated with high mortality rates. This project will provide global and fundamental insights into our understanding of why IAV often cause fatal disease. It will advance knowledge of the mechanisms by which the host and virus interact and elucidate how the host's immune system responds to the infection and modulates disease, to facilitate the development of improved treatments for severe IAV infections.
A New Monocyte Atherogenic Phenotype In Chronic HIV Disease.
Funder
National Health and Medical Research Council
Funding Amount
$632,037.00
Summary
Most HIV+ people in Australia now die from cardiovascular disease, caused by atherosclerosis or thickening of coronary arteries. The ability of a white blood cell called the monocyte to prevent atherosclerosis is impaired in HIV. This project aims to understand how HIV does this and how we can reverse the effect. Understanding these processes will also help improve treatments to reduce heart disease in people with other chronic inflammatory conditions.
Inhibition Of IFN-?/? By Human Metapneumovirus And The Induction Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$605,251.00
Summary
The newly isolated human metapneumovirus (hMPV) causes significant respiratory illness in infants, young children and the elderly. The virus can persist long-term and may predispose individuals to chronic lung disease. This proposal aims to determine the mechanisms by which hMPV infection causes respiratory disease, with a view to improving treatments and preventing disease.
The Role Of CXCR3 Chemokines In Hepatitis C And Other Forms Of Viral Hepatitis
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 10-20 years. This liver disease is primarily a result of the host immune response to liver cells (hepatocytes) infected with HCV. As part of this immune response there in an increase in the number of immune cells that infiltrate the liver. To date we do not fully understand the mechanims that attract these cells to the liver but a class of molecules called chemokines is the ....The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 10-20 years. This liver disease is primarily a result of the host immune response to liver cells (hepatocytes) infected with HCV. As part of this immune response there in an increase in the number of immune cells that infiltrate the liver. To date we do not fully understand the mechanims that attract these cells to the liver but a class of molecules called chemokines is the most likely candidate. Thus a greater understanding of the chemokines expressed in the liver, their modulation and role in attracting immune cells to the liver in HCV-related liver disease will help us understand the basic mechanisms of liver disease with the possibility of development of novel therapeutic strategies. In pilot studies we have shown that the chemokine interferon-inducible T cell alpha chemoattractant (I-TAC) is significantly increased in the liver of persons infected with HCV. I-TAC is a member of the CXCR3 ligand chemokine family that attracts lymphocytes to sites of inflammation and as such may play an important role in hepatitis C. We have also shown that hepatocytes express I-TAC and that HCV can upregulate expression of I-TAC in a laboratory model of HCV replication. This proposal plans to determine the molecular mechanisms of I-TAC expression in response to HCV replication and to investigate if I-TAC expression is unique for hepatits C or a general feature of viral infections of the liver. We also plan to determine the the role of I-TAC and other CXCR3 ligand family members in a mouse model of viral hepatitis through the use of CXCR3 ligand antagonists. These experiments will enhance or knowledge of the role of the CXCR3 ligands in hepatitis C and viral hepatitis in general.Read moreRead less
The Role Of Innate Inflammatory Responses In Viral Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$782,514.00
Summary
Viruses are known to cause arthritis (HIV, hepatitis viruses, mosquito borne viruses). Symptoms of viral arthritis include joint pain, stiffness, and swelling. The mechanism of disease is poorly understood. We have developed a novel animal model of disease and human cell culture models by which to study disease caused by viral infections. This models provide an excellent opportunity to explore the mechanisms of rheumatic disease in a functioning animal and to explore new treatment regimes.
Morbidity and mortality secondary to liver disease is greatly increased in people co-infected with HIV and HBV compared to those infected with HBV alone. Mortality remains elevated even after treating both viruses. This project will investigate the mechanism of how HIV accelerates liver disease in patients co-infected with HBV. We hypothesize that this occurs by combined effects of HIV and HBV on inflammation in the liver. These studies could potentially lead to new treatments for liver disease.