HIV Genome = Revealed!

Researchers from North Carolina, USA, have decoded the genome structure of the Human Immunodeficiency Virus (HIV), the virus that causes AIDS. The genome, which carries its information as RNA, is composed of two separate strands, of nearly 10,000 nucleotides each. On top of this, the intricate structures that these strands form are often difficult and painstaking to analyze. In fact, up until now they have only ever been partially modeled, and always in small regions. Now that this has changed, it could well represent a change in the ability of modern medicine to fight and possibility to control viruses as dangerous as HIV.

The RNA structure has been found to influence many important steps in the infectivity cycle of HIV. Such information can be used to help scientists understand how the human host is tricked into ignoring the presence of the virus, which can make early detection and medication possible. An understanding of exactly what we are dealing with can also lead to scientists modifying the sequence of the virus, and seeing what changes affect its growth. This can help to ascertain what segments of the genome are the most important to the virus, which can give us an indication of possible weaknesses.

These results will have considerable implications for the understanding of human viruses, and are expected to accelerate further research into the development of future antiviral drugs.

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Reference:
http://www.sciencedaily.com/releases/2009/08/090805133015.htm

One shot treatment for HIV?

In February this year, the remarkable case of a man “cured” of HIV following a bone-marrow transplant was published in the New England Journal of Biology. The naturally resistant bone marrow donor has inherited a copy of the 'delta32' mutation from each parent in the CCR5 gene, which inhibits the production of a protein on the outside of CD4 white blood cells which is utilized by the retrovirus to gain access to the cell. By halting production of these 'door handle' proteins the virus cannot establish itself; indeed, according to Gero Hütter of the Charité University of Medicine in Berlin, "it's now almost exactly two years ago that we treated [the patient], and the virus is nowhere to be seen" (Hutter in Coghlan, 2009). However, like the antiretroviral therapies (ART) and vaccine attempts, problems persist in this form of treatment. Chiefly, it is difficult to find a compatible donor, that is, a person with the specific mutations protecting them against HIV. Secondly, the patient had been undergoing chemotherapy as treatment for leukemia so, "every new immune cell that grew thereafter in the bone marrow had these deletions, and so was resistant" (Hutter in Coghlan, 2009), yet this transplant would not be suitable for those with a still-functioning immune system.

It is for these reasons that great promise rests in gene therapy, employing similar principles to the transplant method without the donor requirement. The first human trials of gene therapy conducted by Sangamo Biosciences in California began in February. An artificial version of the naturally occurring enzyme Zinc-Finger-Nuclease (ZFN) is synthesised by the lab and then inserted into a patient's extracted and isolated CD4 cells via viral transduction. The nuclease splices specific sequences in the CCR5 gene discussed earlier so that the membrane protein is not produced thus disallowing HIV to enter the transformed cells. The cells, with ZFN and virus 'washed away', are then reintroduced into the body and should live longer than infected cells, proliferating and gradually overtaking non-resistant CD4 cells so that the patient should no longer suffer the symptoms of HIV; and “this is exactly what happened when Sangamo researchers gave HIV-infected mice altered CD4 cells” (Coghlan, 2009). Other research institutions such as the University of California are looking at using stem cells (CD34) instead of the more specific CD4 cells and inserting ribozymes to stop HIV controlling infected cells at the pre-mRNA stage or a combination of both.

More than 30 million people are living with HIV/AIDS. Bone marrow transplants have shown its possible to protect the patient “if you replace patients' immune cells” says Philip Gregory of Sangamo. The three gene therapies outlined above, although in early stages of development have shown that there is indeed a possibility of a 'one-shot' treatment for HIV.

Coghlan, A. Gene Therapy Promises One-Shot Treatment for HIV. New Scientist. Issue 2696, 02.09.