Assembly Functions Of Respiratory Syncytial Virus Matrix Protein
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory infections (pneumonia and bronchiolitis) in young infants. In addition to the morbidity of RSV infection itself, it is well established that symptomatic RSV infection in infancy predisposes to asthma later in life. As all infants are infected by RSV at least once by age 2 yrs, this virus represents a major public health problem. Additionally, re-infection by RSV is increasingly being recognized as a cause o ....Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory infections (pneumonia and bronchiolitis) in young infants. In addition to the morbidity of RSV infection itself, it is well established that symptomatic RSV infection in infancy predisposes to asthma later in life. As all infants are infected by RSV at least once by age 2 yrs, this virus represents a major public health problem. Additionally, re-infection by RSV is increasingly being recognized as a cause of severe lower respiratory disease in the elderly and in immunocompromised patients. The goal of this research is to understand better the mechanisms used by RSV to replicate itself in mammalian cells. Information from this work could be used to design novel antiviral drugs to treat RSV, and novel attenuating mutations that may assist in developing live RSV vaccines. The research focuses on a key viral protein, the matrix (M) protein, which is involved in many steps in virus replication. We aim to understand how M protein interacts with other components of the virus (specifically, envelope proteins) to orchestrate virus assembly. To coordinate assembly of new virus particles, M protein binds to portions of virus envelope glycoproteins and to RSV nucleocapsids (the internal machinery of the virus), bringing them together at the cell membrane. The protein-protein interactions which are responsible for these functions of RSV M protein will be determined.Read moreRead less
Structure And Function Of Hepatitis C Virus Glycoproteins
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Hepatitis C Virus infects approximately 200 million people world-wide and is the major cause of liver transplantation in the Western world. At present there is no vaccine and interferon alpha is the only therapy available and has only limited success in clearing viral infection. HCV is distantly related to flaviviruses eg tick-borne encephaltitis virus and yellow fever virus. All viruses attach to target cells using receptors to initiate the infection process. In the case of HCV, the envelope gl ....Hepatitis C Virus infects approximately 200 million people world-wide and is the major cause of liver transplantation in the Western world. At present there is no vaccine and interferon alpha is the only therapy available and has only limited success in clearing viral infection. HCV is distantly related to flaviviruses eg tick-borne encephaltitis virus and yellow fever virus. All viruses attach to target cells using receptors to initiate the infection process. In the case of HCV, the envelope glycoproteins interact with as yet unknown receptors on the target cell surface resulting in the virus being internalized into endosomes. It is believed that the low pH environment of these endosomes triggers fusion of the viral and cellular membranes. After fusion the genome of the virus is released into target cells and begins the replication process. The actual events intitiating these processes are not understood for HCV but are believed to be mediated using two envelope glycoproteins. In this project we seek to gain a greater understanding of how viral fusion and entry occurs. We have new information regarding the localisation of the two envelope glycoproteins that will now enable us to carefully examine how viral fusion occurs. Using biochemical approaches, we will study their structure and function and examine how this relates to the well understood flavivirus mode of fusion and entry. We will test the functional consequences of altering the structure of the HCV envelope glycoproteins by developing in vitro assays of HCV fusion. Assays for HCV fusion are essential for future studies to identify viral receptors, examine the role of antibody in viral neutralization and can be used to test novel inhibitors of viral fusion and entry.Read moreRead less
Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries in tropical and subtropical regions. Infection with Dengue viruses cause Dengue fever or its more severe and sometimes fatal form, Dengue hemmorrhagic fever-Dengue shock syndrome (DHF-DSS). Up to 100 million people are infected annually making Dengue virus one of the most important and frequent mosquito-borne viral diseases worldwide. Over the past two decades, the incidence of Dengue virus infectio ....Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries in tropical and subtropical regions. Infection with Dengue viruses cause Dengue fever or its more severe and sometimes fatal form, Dengue hemmorrhagic fever-Dengue shock syndrome (DHF-DSS). Up to 100 million people are infected annually making Dengue virus one of the most important and frequent mosquito-borne viral diseases worldwide. Over the past two decades, the incidence of Dengue virus infection has increased steadily. More than 40% of the world's population is at risk of infection and this number is expected to increase as more people travel. This proposal focuses on the way dengue virus enters cells, specifically the mechanism used by viral proteins to mediate fusion of the viral membrane with that of the host cell. A clearer understanding of the molecular basis of this process should provide potential targets for new drugs that can bind and block this process. In addition, we will also use this information in the design and generation of new vaccine candidates.Read moreRead less