Transport And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$592,023.00
Summary
Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transpor ....Herpes simplex virus (HSV) enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how HSV is transported within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins and how the virus escapes from nerves to infect skin and cause disease. Such information on viral transport will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities. Finally this data will assist in understanding similar mechanisms for other viruses transported in nerve cells such as those causing shingles and rabies.Read moreRead less
The occcurence of herpes simplex virus (HSV) in the general population is very high (up to 60%). In Central Africa, co-infection of HSV and HIV may increase HIV transmission in more than 40% of cases. HSV enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transpo ....The occcurence of herpes simplex virus (HSV) in the general population is very high (up to 60%). In Central Africa, co-infection of HSV and HIV may increase HIV transmission in more than 40% of cases. HSV enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this project is to determine how HSV is assembled within cells at the molecular level. This will lead to identification of crucial molecular interactions required for viral assembly. Such information on viral assembly will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. These antiviral agents will be able to target key viral molecular interactions in essentially all types of cells in the body and act against other herpesviruses in general.Read moreRead less
Functional Roles Of The Tegument Proteins Of Herpes Simplex Virus Type 1
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
The occurrence of herpes simplex virus (HSV) in the general population is very high (up to 60%). HSV enters the human body via the skin before entering nerve cells where it lies dormant in most people. Intermittently the virus reactivates and usually forms blisters at the skin when it sheds. The aim of this project is to define a molecular interaction network at the protein level during the course of infection of a host cell. This information will provide new targets for design of antivirals.
Several members of the Flaviviridae family are major pathogens of humans including dengue (DEN), yellow fever (YF), tick-borne encephalitis (TBE), Murray valley encephalitis (MVE), Japanese encephalitis (JE), and hepatitis C virus (HCV). An Australian flavivirus Kunjin (KUN), however, appears to be naturally attenuated and does not cause an overt disease in humans. In contrast, genetically and antigenically closely related to KUN, New York strain of West Nile virus (NY WN) has already caused ~50 ....Several members of the Flaviviridae family are major pathogens of humans including dengue (DEN), yellow fever (YF), tick-borne encephalitis (TBE), Murray valley encephalitis (MVE), Japanese encephalitis (JE), and hepatitis C virus (HCV). An Australian flavivirus Kunjin (KUN), however, appears to be naturally attenuated and does not cause an overt disease in humans. In contrast, genetically and antigenically closely related to KUN, New York strain of West Nile virus (NY WN) has already caused ~500 deaths and over 20,000 registered infections since its emergence in North America in 1999, including 223 deaths and 9122 infections in 2003 alone. Recent studies with DEN indicated that flaviviruses may interfere with early steps of IFN-signalling pathway. The type I Interferon (IFN) response is the first line of defence against viral infections and many viruses have developed different strategies to counteract this response in order to ensure their survival in the infected host. In this grant we seek to exploit our extensive understanding of the molecular biology of KUN virus and the contrasting behaviour of KUN and NY WN viruses to gain an understanding of the role of flavivirus-mediated suppression of host anti-viral IFN response in virus-host relationships and its importance in determining virus virulence.Read moreRead less
The Human Eukaryotic Translation Elongation Factor 1A Is A Paramyxovirus Virus Dependency Factor
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
Several paramyxoviruses cause respiratory disease in infants, young children and the elderly worldwide. Another paramyxovirus that can be contracted by people from infected horses, Hendra virus, is often fatal. There are currently no vaccines against these viruses, and treatment is generally limited to relief of symptoms. In this project we will uncover how these viruses use human proteins for their growth inside cells, with an aim to develop novel therapeutic strategies.
Host Metabolism And Responses Contributing To Flavivirus Replication And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$592,772.00
Summary
We aim to determine how viruses affect the cells they infect, In particular how they can alter the metabolism and balance of lipids in cells and how this impacts the bodies capability to respond immunologically. We believe that by understanding these basic principles we can target ares fr antiviral therapeutic potential.
Inhibitors Of West Nile Virus Protease As Antiviral Drugs
Funder
National Health and Medical Research Council
Funding Amount
$590,740.00
Summary
The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in people i ....The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in people in the Middle East, parts of Africa and Europe, but recent epidemics in Israel (1998), Romania (1996), United States (1999), and UK (2003), that have been traced to migratory birds, were characterized by severe symptoms , severe neurological pathology, and fatalities. In the USA alone there were 4,156 infections and 284 deaths in 2002, 9122 infections and 223 deaths in 2003, and this mosquito borne virus has quickly spread since 1999 through all USA states and into Canada and Mexico (http:--www.cdc.gov-ncidod-dvbid- westnile-index.htm). No treatments or vaccines are available. This project focuses on a viral enzyme, known as the West Nile Virus NS3 protease, that is essential for replication of the virus. By studying the enzyme in the laboratory we can design small molecules that block its function and these are potential leads for developing drug treatments for people infected, not only by this virus but potentially also other flaviviruses. A precedent is the success of inhibitors of HIV-1 protease that are the most effective treatment for humans with HIV-infections, and other viral proteases are now becoming recognized as viable antiviral targets for pharmaceutical development. The project involves experts on small molecule protease inhibitor design and development, proteases, and virology including West Nile virology. We expect to generate new information at the cutting edge of West Nile Virus and flavivirus research and promising new antiviral drug candidates.Read moreRead less
Hepatitis B Virus Drug Resistance: Impact On The Immunisation Program
Funder
National Health and Medical Research Council
Funding Amount
$113,322.00
Summary
ñAntiviral drug-associated vaccine escape mutantsî have the potential to jeopardize the hepatitis B immunization program. Which particular viral mutations or combination of mutations that can directly affect the clinical outcome of infection, especially in the context of vaccine induced immunity, are not known. In this study we will identify the clinical sequelae and public health consequences arising from the selection of these mutants.
Viral Factors Involved In Flavivirus Replication And Virus-host Interactions
Funder
National Health and Medical Research Council
Funding Amount
$743,696.00
Summary
With our increased understanding of virus-host interactions it has become apparent that small, non-structural proteins and small RNAs of most viruses are vital for numerous, often multiple, functions in the viral life cycle. In the proposed project, we seek to gain a detailed understanding of the functions of small nonstructural protein NS2A and small abundant viral RNAs of medicaly important encephalitic flaviviruses, which have remained so far elusive and are at the cutting-edge in the researc ....With our increased understanding of virus-host interactions it has become apparent that small, non-structural proteins and small RNAs of most viruses are vital for numerous, often multiple, functions in the viral life cycle. In the proposed project, we seek to gain a detailed understanding of the functions of small nonstructural protein NS2A and small abundant viral RNAs of medicaly important encephalitic flaviviruses, which have remained so far elusive and are at the cutting-edge in the research field. We anticipate that with a better understanding of the roles of these factors in flaviviral replication and pathogenesis, novel targets for antiviral therapies and-or molecular determinants for inclusion in candidate vaccines will be identified.Read moreRead less