HPV And Cervical Carcinoma: Signaling And Clinical Responses To Interferons
Funder
National Health and Medical Research Council
Funding Amount
$534,480.00
Summary
Cervical carcinoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers caused by the wart virus. However, results of recent work indicates that viruses like the wart virus, HPV, have developed ways of inhibiting its eff ....Cervical carcinoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers caused by the wart virus. However, results of recent work indicates that viruses like the wart virus, HPV, have developed ways of inhibiting its effectiveness. We have found that cervical carcinoma cells and virally infected cells resist the direct anti-cancer and anti-viral effects of interferons because they have abnormalities in their ability to respond to interferon. We have made good progress in understanding why these cells do not respond to the interferons. In particular they show a deficiency in the activity of cell proteins required to transmit the interferon signal inside the cells. The current proposal will allow us to gain a greater understanding of the processes inside cells that are taken over by the wart viral proteins and the reasons for its abnormality in interferon resistant cancer cells. We will determine whether the levels of certain genes in clinical samples from patients relates to their response to interferon treatment. This may allow us to establish a test to predict which patients will respond to interferon therapy, saving patients from ineffective treatment, side effects and cost. This study will have a broad significance to many human diseases where abnormalities in interferon signaling occur and will help to bring about the necessary changes in cell properties to overcome the abnormalities, restore the responses and improve the application of interferons to treat infectious diseases and perhaps other cancers as well.Read moreRead less
Anogenital Human Papillomavirus Infection And Its Outcomes In Men
Funder
National Health and Medical Research Council
Funding Amount
$333,433.00
Summary
Anal human papillomavirus (HPV) infection is common in homosexual men. Low risk types cause anal warts and high risk types of HPV cause anal cancer. This study will determine incidence and risk factors for HPV infection in a cohort of young homosexual men, the association of anal warts treatment with HIV risk, and the specific association of HPV subtypes with anal cancer. The findings of this research will help delineate the potential benefits of HPV vaccination in this population.
A Phase 1b Trial Of Specific Immunotherapy For Recurrent Respiratory Papillomatosis
Funder
National Health and Medical Research Council
Funding Amount
$141,208.00
Summary
This project will determine whether immunisation can be used to effectively treat an existing infection. To date, immunisation has only been used to prevent infection, but there are many chronic infections where intervention might help the body's defences to to a better job and clear the chronic infection. In this study, we will work out whether this approach can be applied to a virus infection ( papillomavirus) which is associated with cancer. We will test immunisation against a chronic and lif ....This project will determine whether immunisation can be used to effectively treat an existing infection. To date, immunisation has only been used to prevent infection, but there are many chronic infections where intervention might help the body's defences to to a better job and clear the chronic infection. In this study, we will work out whether this approach can be applied to a virus infection ( papillomavirus) which is associated with cancer. We will test immunisation against a chronic and lifethreatening disorder in which warts grow in the respirarory tract, as there is currently no satisfactory treatment for this. If the project is successful we may also learn which blood tests are likely to predict the outcome of immunisation to treat infection.Read moreRead less
Herpesviruses infect most Australians and cause recurrent ulcers, birth defects and cancer. Infection lasts lifelong, and spreads to close contacts without obvious clinical signs. Thus disease is hard to prevent. However we can learn much from related animal infections. We have shown that both mouse and human herpesviruses enter mice via cells in the nose. Thus human infections might follow the same route. We will define what body defences work here and whether vaccines can prevent infection.
Human ?-herpesviruses persist for life, cause cancers and emerge with particular virulence when the immune system is weak. Vaccination against them is therefore an important health priority. We have shown for a related ?-herpesvirus of mice that live vaccines protect. Antibody seems to play a major role. We will test whether safer, recombinant vaccines are also sufficient to elicit protective antibody. Thus we can establish a viable strategy for preventing virus-induced human cancers.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
Defining The Requirement For The Inhibition Of Bak To The Pathogenesis Of Cytomegalovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
Apoptosis, or programmed cell death is a powerful defence mechanism against viral infection. Thus, to replicate efficiently viruses have evolved means to inhibit apoptosis. The central aim of this work is to understand how cytomegalovirus prevents cell death protein during infection. The proposed studies will improve our understanding of the mechanisms that regulate viral replication and will contribute insights into the normal processes that control cell survival.
Influenza A Virus PB1-F2 Protein: A Putative Virulence Factor And Initiator Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$474,718.00
Summary
Influenza virus produces a protein of undefined function called PB1-F2. Infection of mice with virus expressing PB1-F2 from virulent strains causes severe lung inflammation, while PB1-F2 from milder seasonal viruses does not. We will examine how PB1-F2 influences virulence of human influenza in the ferret, which exhibits the same illness as humans. This work will help understand the disease severity of newly evolved influenza viruses of humans and the role of PB1-F2 in mediating this.
Understanding HIV Resistance To Entry Inhibitors To Advance The Development Of Novel Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$877,585.00
Summary
We cannot afford to be complacent in the search for improved anti HIV drugs for 2 principal reasons; First, worldwide a staggering 66% of infected individuals who need treatment are still unable to access therapy; and Second, the main reason why most treated patients are now living longer and more healthy lives is because we have never stopped developing newer therapies to provide options for patients. In this study we will develop and test newer drugs that block HIV infection of cells.