How HIV Hijacks The Immune System

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    A 3-D model of HIV peeled back to show its layers. HIV's genetic material sits inside a spherical shell (gray matrix) studded with spikes (dark gray and orange). The sphere pops open when a T cell tugs on a spike.
    Courtesy of Ivan Konstantinov/© Visual Science 2011
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    HIV is thought to originate from simian immunodeficiency virus, also known as the African Green Monkey virus. As for HIV, the genes of SIV are encased in a shell with spikes that help it invade a cell. This 3-D model was obtained by cryo-electron tomography.
    Sriram Subramaniam and Donald Bliss/PLoS Pathogens
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    On the left, one HIV spike seen on the virus' surface. When it bumps into a T cell, a finger-like projection on the cell's surface, called CCR5, pushes down on the spike. This interaction pops open the HIV and releases the infectious genes into the cell. A gene therapy could protect T cells by inactivating the CCR5 gene.
    Courtesy of Sriram Subramaniam /Nature
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    An artistic rendering of an immune cell, illustrating the petal-like sheets on its surface.
    Courtesy of Sriram Subramaniam and Donald Bliss /NIH
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    HIV particles (red spheres) pool in deep crevices on the surface of an immune cell. Some scientist think that HIV can move quickly around the immune system by hiding out in these nooks and crannies.
    Sriram Subramaniam and Donald Bliss /PLoS Pathogens
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    Here a T cell (yellow) reaches into the surface of another immune cell (pink) to grab HIV particles (red circles). This image was obtained by electron tomography.
    Courtesy of Sriram Subramaniam and Donald Bliss /NIH

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The road to a cure for AIDS is in sight, even if every step on the journey isn't clear yet.

One of the most promising avenues is a kind of gene therapy that would block HIV's entry into cells of the immune system. A genetic tweak could make these key cells resistant to the virus's attack.

"HIV is like a jack-in-the-box," says Sriram Subramaniam, a biophysicist at the National Cancer Institute who peers at HIV with electron microscopes.

The virus's genetic material sits inside a shell that is studded with spikes. To infect a cell, the shell has to pop open and release the virus's genes into the cell.

That's what happens when HIV bumps into T cells, the white blood cells that are the virus's prime targets.

T cells are studded with finger-like projections, including one called CCR5 that fits on HIV's spikes.

A gene therapy now being tested in people takes the CCR5 receptor out of their T cells. Without CCR5, the cells don't trigger the virus's jack-in-the-box invasion. If the virus can't get inside the cells, it can't reproduce.

A few people, mainly Caucasians, lack CCR5 because of genetic mutations. And one man who received bone marrow transplants for leukemia from a donor without CCR5 receptors has been cured of HIV/AIDS, his doctors say.

Separately, Subramaniam has found evidence that HIV hide in other places in the immune system even before it enters cells.

Using a microscopy technique to create 3-D models of cell surfaces, he and his team saw some immune cells took on flower-like shapes. HIV can hide in crevices between the large petal-like sheets.

These pools of HIV may help the virus's move around the immune system, Subramaniam tells Shots.

The virus gets a free ride as these cells move through the blood. "T cells can reach deep into these channels to pick up the HIV itself," says Subramaniam.



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