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Research Seeks a Way to Destroy HIV Protein Shield

February 21, 2012

In November, the Bill & Melinda Gates Foundation announced it had awarded nine new Grand Challenges Explorations Phase II grants, one of them to Andy Qigui Yu, M.D., Ph.D., assistant professor of microbiology and immunology at the Indiana University (IU) School of Medicine. The Phase II grants were awarded to researchers who had received initial $100,000 awards and had shown promising results.

Now in laboratories at IU, Dr. Yu is testing a promising compound that may counteract HIV's ability to hijack the immune system's protection mechanism, according to a February 13 report in ScienceDaily.

In the immune system, initial HIV infection causes the body to release antibodies that attack the virus, and some HIV is destroyed. But HIV is able to quickly defend itself by co-opting a part of the innate immune system called the complement. The complement includes a vital mechanism that prevents immune system cells from attacking the body's own cells. HIV is able to use a key protein in that self-protection mechanism, CD59, and thus disguises itself as one of the body's normal cells, not an infective viral cell.

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"HIV is very clever. As it replicates inside cells, it takes on the CD59. The virus is covered with CD59, so the immune system treats the virus like your own normal cells," Dr. Yu said.

The new grant will support not only Dr. Yu's research into compounds that may block the ability of HIV to hide behind the CD59 "cloak," but also his work to identify the mechanism the virus uses to incorporate CD59.

"If we find that mechanism, then we can develop something to block that incorporation, and HIV may lose that protection from the immune system," Dr. Yu said.

Researchers have been able in the past to generate antibodies that successfully attacked HIV in the laboratory. But these antibodies have failed in human testing because the virus in the body escapes from immune system attacks, Dr. Yu said.

In an attempt to disrupt HIV's hijacking of CD59, Yu and colleagues at IU and Harvard University crafted a molecule from a bacterial toxin that is known to bind to the CD59 protein. In laboratory tests, they administered the molecule to blood samples taken from patients with HIV. The bacteria toxin molecule latched on to the CD59 proteins, revealing the viral particles to be invaders and enabling the antibodies to attack the virus.

The recent experiments have indicated that the administration of the molecule enabled the antibody-complement to attack infected cells and not just the virus particles found in the blood samples. The next steps will include more extensive testing of the molecule in a broader range of patient samples, Dr. Yu said.



  
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This article was provided by Positively Aware. It is a part of the publication Positively Aware. Visit Positively Aware's website to find out more about the publication.
 
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