Modulation Of Apoptosis By Cytomegalovirus: Analysis Of New Mechanisms To Interfere With Cytomegalovirus-induced Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,084.00
Summary
Apoptosis, or programmed cell death is an essential process in developmental and homeostatic control of complex biological systems. In addition to these primary house keeping roles, apoptosis provides a powerful defence mechanism against invading pathogens, such as viruses, since it allows early elimination of infected cells from the host. A basic property of herpesviruses is their ability to establish persistent infection and remain in association with the host for its lifetime. This strongly u ....Apoptosis, or programmed cell death is an essential process in developmental and homeostatic control of complex biological systems. In addition to these primary house keeping roles, apoptosis provides a powerful defence mechanism against invading pathogens, such as viruses, since it allows early elimination of infected cells from the host. A basic property of herpesviruses is their ability to establish persistent infection and remain in association with the host for its lifetime. This strongly underlines their success at reaching an accommodation with the immune system's anti-apoptotic mechanisms. The central hypothesis of this project is that herpesviruses, such as murine and human cytomegalovirus, encode proteins that interfere with cell death pathways thereby circumventing host defence so that viral replication and dissemination can proceed. Thus, the aims are to identify and characterise cytomegalovirus proteins that modulate apoptosis. These studies will improve our understanding of the control of apoptosis during viral infection, especially as caused by cytomegaloviruses. Human cytomegalovirus (HCMV) is a pathogen able to cause significant morbidity and mortality in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. Hence, the proposed studies will allow the elucidation of molecular mechanisms that may be relevant to the pathogenesis of HCMV in man and will provide insights into the rational design of suitable antiviral drugs and vaccines. Understanding viral mechanisms of host immune evasion continues to improve our understanding of complex cellular pathways. Therefore, given that abnormal regulation of apoptosis is implicated in the development of degenerative conditions, cancer and autoimmune disease, the proposed studies will provide valuable insight towards the development of new therapies for these pathological conditions.Read moreRead less
Role Of Cytomegalovirus Class I Homologue In Interference With Host NK Cell Responses - A Potential Antiviral Target
Funder
National Health and Medical Research Council
Funding Amount
$428,020.00
Summary
A common property of herpesviruses such as cytomegalovirus is their ability to establish lifelong infection in their hosts. In humans, cytomegalovirus infection can lead to tissue damage in normal individuals and may cause severe disease and even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The ability of these viruses to establish persistent infection and remain in asso ....A common property of herpesviruses such as cytomegalovirus is their ability to establish lifelong infection in their hosts. In humans, cytomegalovirus infection can lead to tissue damage in normal individuals and may cause severe disease and even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The ability of these viruses to establish persistent infection and remain in association with the host for its lifetime is a consequence of their capacity to subvert normal host immune responses. This is achieved by destroying or mimicking the functions of molecules and-or pathways critical to normal host defence mechanisms. The viral gene product under investigation is similar to a cellular protein critical for the ability of immune cells to kill foreign and-or infectious agents. We will investigate the mechanisms by which this viral gene product interferes with the host's first line of defence against viral pathogens. The proposed studies will improve our understanding of the strategies used by viruses to escape normal host immune responses and hence provide insights into the rational design of antiviral drugs and vaccines. Since the viral protein under investigation is similar to a cellular protein essential for the ability of immune cells to kill foreign or infectious agents, an improved understanding of the mechanisms of action of this protein will continue to improve our understanding of cellular events which play a crucial role in immune responses involved not only in control of infection, but also in tumour growth and transplant survival. Thus, the proposed studies will provide valuable insight towards the development of new therapies for pathological conditions associated with the above.Read moreRead less