A new strategy to fight HIV and AIDS

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March 7th, 2008

A new strategy to fight HIV and AIDS

Posted by Roland Piquepaille @ 10:13 am

An international team of researchers has developed a novel strategy

against HIV. They added two genes to immune cells which `transformed

them into potent weapons that destroy cells infected with HIV, the

virus that causes AIDS.' This idea of `genetically engineering immune

cells to redirect their infection-fighting ability toward killing HIV-

infected cells could lead to an entirely new approach for combating

AIDS.' This research looks promising, but it's only working in labs

right now. But read more…

This research project has been led by Dr. Goldstein, Director

of the Einstein/MMC Center for AIDS Research (CFAR). Here is a link

to his research objectives. But Goldstein was not alone to work on

this study. There were other Einstein researchers involved as well as

scientists and doctors of Harvard Medical School, the VU University

Medical Center of Amsterdam, in the Netherlands, and St. Jude

Children's Hospital in Memphis, Tennessee.

Before going further, here is how HIV works. " After infecting a cell,

HIV instructs it to make viral proteins. Tiny bits of these proteins,

known as peptides, are displayed on the surface of the infected cell—

the cell's way of signaling the immune system that it is infected.

Detecting virus-infected cells so they can then be eliminated is the

job of CTLs and the protein molecules, known as T-cell receptors,

that jut from their surface. If a CTL's T-cell receptor has the right

amino acid sequence, it will recognize the HIV peptide on the

infected cell as foreign — prompting the CTL to multiply and attack

the infected cell. But all too often, this battle between activated

CTLs and HIV-infected cells ends badly. Why, then, are super CTLs of

elite controllers so effective in killing HIV-infected cells? "

After searching an answer to this question, the researchers decided

to `reprogram' these CTLs by inserting specific genes into their

chromosomes. " `We demonstrated that these genetically reprogrammed

CTLs have very strong activity in terms of killing HIV-infected cells

in both test tubes and an animal model,' says Dr. Goldstein. In some

of the animal studies, for example, the researchers injected mice

with both HIV-infected human cells and with reprogrammed naïve CTLs

into which the HIV-recognizing T-cell receptor genes had been

inserted using the lentiviral delivery system. One week later, when

the researchers looked for HIV-infected human cells in the animals,

they found that the infected cells had virtually been eliminated. "

If this technique works with animals, will it work for humans? Here

are some Goldstein's ideas about the future. " `Ultimately, we'd like

to remove CTLs from patients, convert them into potent HIV-specific

CTLs by inserting a variety of HIV-specific CTL receptor genes, and

then re-infuse these fresh, genetically reprogrammed CTLs back into

patients. By reinforcing the immune system in this way, we hope to

turn the tide of battle against HIV in favor of people infected with

the virus.' "

In other words, even the lead researcher doesn't really know if this

technique will work on people infected by HIV.

For more information, this research work has been published in The

Journal of Virology under the very long title " Lentiviral Vectors

Encoding Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell

Receptor Genes Efficiently Convert Peripheral Blood CD8 T Lymphocytes

into Cytotoxic T Lymphocytes with Potent In Vitro and In Vivo HIV-1-

Specific Inhibitory Activity " (Volume 82, Issue 6, Pages 3078-3089,

March 2008). Here is a link to the abstract which is undertandable

only by experts in the field.

Sources: Albert Einstein College of Medicine news release, March 4,

2008; and various websites