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What is responsible for the long-term survival of some HIV positive patients?
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Ongoing research involving the study of the various causes and possible therapeutics for HIV infection has helped in the detailed study of the life cycle of the HIV retrovirus, as well as the progression of the HIV infection within the body leading to the most dreaded disease of AIDS (Autoimmune Deficiency Syndrome) in most of the cases. However, the study has revealed that in some HIV positive patients, the infection has delayed progression or in some cases non-progression leading to increased mortality of such patients.

Research to find out the main reason for the long-term survival of such patients has shown the role of the innate defense mechanism of the patients, which helps them survive for a longer time in spite of being infected with the HIV virus even without undergoing any sort of treatment. The presence of a particular key enzyme in the white blood cells of some patients has helped in their long-term survival. The study of nature and properties of this enzyme has become a raging topic of research, which may help in the development of new area of therapeutics for the HIV positive patients.

Among the HIV positive patients, a very small percentage around 5% almost do not develop full-fledged AIDS or develop in a delayed manner. The presence of the enzyme APOBEC-3G (A3G) in higher levels in the white blood cells of such patients has helped the patients in preventing the progression of the infection. The recent studies with human cells have confirmed the role of A3G in non-progression of the infection in some patients.

Researchers have proved the role of A3G in editing the genetic code of HIV[b] introducing changes with every replication cycle of the retrovirus. These changes introduced within the virus causes [b]corruption of its genetic code, thereby preventing its reproduction. However, the HIV has also evolved to produce a protein known as the Viral infectivity factor (Vif), to counter the attack of A3G. The Vif grabs the A3G and initiates the destruction of A3G by the body itself by tricking it. The destruction of A3G, the editing enzyme, helps the progression of the HIV infection, which ultimately attacks the immune system of the patient making them vulnerable to the development of AIDS resulting in death.

The absence of sufficient levels of A3G in most of the patients causes progression of the HIV infection, as the Vif secreted by the virus does not have enough A3G to overcome its effects and prevent its progression. Hence, studies are being conducted to devise methods to prevent the Vif from destroying the A3G produced, even if they are of low levels.

Extensive research is going on to unleash the mechanism involved in the mechanism of A3G and to prove its role in the progression of the infection in the HIV positive patients. It has been elucidated that in the absence of any sort of antiviral therapy, the A3G does help in causing rapid changes in the viral genetic code preventing the production of the viral proteins and ultimately making the virus unable for reproduction. It was also validated that presence of higher levels of A3G in some of the HIV positive patients studied helped in the delayed progression of the infection in them, while low levels of A3G in other patients caused normal progression of the infection. It was found that higher A3G levels corresponded to lower viral levels of HIV.

It was also reported that higher A3G levels were associated closely with higher counts of CD4 helper T cell. In normal cases, the helper T cells with CD-4 receptors helped the immune system by targeting the bodily invaders; however, the spread of HIV infection resulted in the destruction of the CD-4 helper T cells.

The discovery of A3G has helped in various ways in the HIV related research. It has helped in the development of a prognostic marker in the diagnosis of AIDS with the measurement of A3G in the HIV- infected individuals. It has helped in the study of the underlying mechanism involved in the non-progression or delayed progression of the HIV infection in some patients. Moreover, it has helped in the development of new therapeutics for the HIV infection by devising new methods for the protection of A3G from the viral attack to treat AIDS and other infectious diseases.

The new approach for HIV infection involves exploiting the 14editing enzymes having the property of editing the genetic code of the virus, as novel targets for the development of pharmaceuticals. The main focus is in disabling the action of Vif on A3G. The Vif is a dimer that grabs the A3G with its two arms and causes its destruction. The main aim in is development of drugs that can prevent the dimerization of the Vif and prevent the grabbing of A3G thereby preventing its destruction. A drug candidate, a Vif Dimerization Antagonist (VDA) has been developed by a biotech organization called Oyagen, which has been found to be successful in reducing HIV infectivity in different experiments. However, pre-clinical studies on human trials are essential before the drug candidate can be used in HIV therapeutics in future.
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What is responsible for the long-term survival of some HIV positive patients? - by Kamat2010 - 11-07-2012, 03:13 PM
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What is responsible for the long-term survival of some HIV positive patients?00