HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein transla ....HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein translation from RNA are relatively poorly understood compared with the other control points of cellular gene expression, such as the synthesis of mRNA. This project examines how astrocytes rapidly detect the presence of HIV mRNA and alter their translation machinery to halt the expression of HIV protein. This host defence mechanism involves two key components; the cellular component that identifies and responds to the viral mRNA, and the structural features of the HIV mRNA that enable the cell to detect its viral origin. We will study how translation of HIV proteins requires both HIV and cellular factors. We will determine the impact of both viral RNA elements and viral RNA binding proteins on the translation of viral and cellular proteins. The contribution of the type-1 interferons that are produced in response to viral infection will be studied for their role in augmenting the inhibition of HIV protein translation. Since HIV infected astrocytes significantly contribute to the onset of AIDS dementia, we will sees a strategy to lock HIV into a dormant state in the brain and thereby prevent the neurodegenerative disease associated with HIV. We will use the anti-viral mechanism blocking HIV protein translation in astrocytes to protect other cell populations, such as the CD4+ lymphocytes, from HIV infection. These studies will also give insights into the general mechanisms for translational control of gene expression in human cells.Read moreRead less
Investigation Of Neural Mechanisms Of 670 And 830nm Laser Acupuncture In Pain Relief, Using Rat
Funder
National Health and Medical Research Council
Funding Amount
$326,207.00
Summary
Background Chronic pain is common and costs $10 billion dollars per year in Australia. Drug therapies are widely used but serious side effects limit use. Patients actively seek non-drug treatments and laser acupuncture is one of the most commonly sought therapies for chronic pain, however, how it works is not well understood. Our previous work Researchers propose that laser acupuncture reduces pain by direct effects on nerves, altering how pain signals are transmitted to the brain. To investigat ....Background Chronic pain is common and costs $10 billion dollars per year in Australia. Drug therapies are widely used but serious side effects limit use. Patients actively seek non-drug treatments and laser acupuncture is one of the most commonly sought therapies for chronic pain, however, how it works is not well understood. Our previous work Researchers propose that laser acupuncture reduces pain by direct effects on nerves, altering how pain signals are transmitted to the brain. To investigate this we (CI A and CI B) previously undertook a study of infrared laser on nerve cell cultures. This followed on from a positive clinical study with the same laser wavelength in the treatment of neck pain, undertaken by CI B. We established that laser temporarily interrupts the nerve transport system, which is made up of a series of minute tubes, called microtubules. These act as a “monorail” system for transport of mitochondria, which provide energy for all nerve functions. We propose that temporary interruption of this system, called fast axonal transport, disrupts the conduction of pain signals along the nerve, resulting in pain relief. Important unanswered questions The mechanism by which 830nm laser acupuncture relieves pain clinically remains poorly understood. For its acceptance into mainstream clinical practice it is important to determine the effect of laser on the peripheral nerves and in particular the pain carrying fibres. We know from an earlier study that a single exposure causes significant but reversible changes in pain fibres including axonal microtubule disruption, decrease in mitochondrial membrane potential and block of fast axonal flow. These events would result in conduction failure. The question is whether the repeated irradiations, comparable to those delivered clinically result in the same changes. This would provide a scientific basis for understanding the clinical effectiveness of laser acupuncture. We also do not know if 670nm laser acupuncture would act in the same way. There is evidence that this may be more effective so that this remains another important unanswered question. Further, there is no evidence regarding which wavelength would be cost and time effective as it is desirable to deliver lower dose. We need to determine the most effective dose and wavelength so that clinical trials could be carried out as was done for the trials by CIB (Chow and Barnsley, 2006).Read moreRead less
Enterovirus 71 In The Asia-Pacific Region: Reverse Genetic Approaches To Virus Surveillance And Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$690,833.00
Summary
In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop ....In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop a genetically defined, live attenuated vaccine strain. Candidate vaccine strains will be tested for their effectiveness in both cell culture-based and animal models.Read moreRead less
Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how thi ....Approaches to combat AIDS and its causative agent, the human immunodeficiency virus HIV-1, have thus far proved ineffective. The proposed research program intends to investigate the nuclear import of two HIV-1 proteins which have central roles in HIV infection. We will apply our expertise in the area of the regulation of nuclear import of viral proteins, and build on our observations with respect to these proteins to attempt to establish the mechanistic basis of their nuclear import, and how this differs from the conventional nuclear import pathways used by normal cellular proteins. We already have evidence that nuclear import of HIV-Tat is regulated in novel fashion by cellular factors, and intend, through determining its mechanistic basis, to be able to form the basis of a strategy to block this import pathway specifically, and thereby inhibit HIV replication. This may form the basis in the future of a new pharmaceutical approach to combat HIV-AIDS.Read moreRead less