Cutting Out HIV — Permanently

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HIV. The very mention of it sends chills through many a spine. Things have vastly improved since the early days of HIV (Human Immunodeficiency Virus) and the disease associated with it, AIDS (Acquired Immune Deficiency Syndrome). When HIV is introduced, the body responds by creating antibodies to try and fight the virus. When we test for HIV, we are looking for these antibodies, thus presenting the presence of the virus. (More depth: T Helper Cells are a type of lymphocyte or white blood cell that play a central role in cell-mediated immunity. They are called T cells because they mature in the Thymus. CD4+ T Cells are the primarily attacked cells by the HIV virus, thus causing a decline in number of these CD4+ T Cells, and thus a lowering of the overall immune system).

The prognosis isn’t too bad these days with the current combination anti-retroviral therapy (cART) cocktails to keep infections at bay, thus preventing the disease from progressing to full blown AIDS. Yet, a complete cure has been elusive. The virus DNA makes itself at home in the human genome, and settles in for the long haul, waiting for any opportunity to strike back. This poses a problem for when the virus starts to increase its resistance to the current drugs, and the side effects are no picnic either.

HIV VIRUS
HIV Virus (pic from BBC.COM)

Scientists have now figured out that there may be a way of cutting this lurking virus out of the DNA once and for all. An engineered enzyme that they have forced into targeting a highly conserved (which means it almost always passes down from generation to generation) 34-base pair sequence of genetic code on either side of the HIV DNA sequence. This sequence is found in about 82 percent of the individuals infected with HIV. This enzyme, called BREC1 (or Broad Range Recombinase 1), has historically been involved in snipping a totally different genetic sequence (Cre/loxP). The researchers involved have ‘retro-fitted’ it to look for the HIV 34-base repeat sequence and thus target it for elimination. Once the offending DNA has been excised, the DNA Damage repair enzymes can do their job and splice the ends of ‘good’ DNA back together. Lab testing showed that this process was done without any side effects, whether genotypic (mutations) or phenotypic (outward appearance). They were also able to show success in “humanized” (hu-RAG or human Recombination activating gene) mice where the helper CD4+ T Cells are indicative of the level of disease. As the BREC1 enzyme was introduced into these hu-RAG mice, it showed a progressive decline in HIV infection to the point where there was no more HIV detectable in the remaining human cells that were in the mice.

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The only way of eliminating HIV is to eliminate the virus, and to eliminate the virus we have to eliminate its DNA, preventing it from further duplication and spreading to healthy human cells. Here’s hoping its days are numbered.

[button link=”http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.3467.html” icon=”fa-external-link” side=”left” target=”blank” color=”285b5e” textcolor=”ffffff”]Source: Nature[/button]
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