Human protein able to control HIV - explains long-term non-progression

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Researchers in the US have discovered HIV-inhibiting proteins which may explain why some people’s immune systems are much more effective at controlling HIV.

Called alpha-defensins-1, -2, and -3, the proteins could have major implications for future HIV treatments, according to investigators from the Aaron Diamond AIDS Research Center (ADARC) in a study published in 26 September edition of Science.

Investigators found that CD8 T cells produce high concentrations of alpha-defensin proteins in a small number of people. Significantly, a strong CD8 response is thought to be the reason why a very small percentage of people remain well with no immune damage despite being infected with HIV for decades.

Glossary

CD8

A molecule on the surface of some white blood cells. Some of these cells can kill other cells that are infected with foreign organisms.

protein

A substance which forms the structure of most cells and enzymes.

strain

A variant characterised by a specific genotype.

 

long-term non-progressor

An HIV-infected person who remains free of AIDS symptoms (such as immune system decline or opportunistic diseases) for an unusually long period of time in the absence of treatment. These individuals typically have strong CD8+ T-cell responses, minimal lymph node damage and a relatively low viral load. About 10% of HIV-positive people seem to be long-term non-progressors. Most, but not all, are elite (or HIV) controllers. 

Although it was established in 1995 that a family of proteins called beta-chemokines could account for HIV suppression in some people with no signs of HIV progression, investigators noted that the protein was ineffective against some strains of HIV and was not an adequate explanation for long-term non-progression. However, the alpha-defensins proteins were found by investigators to be effective against all strains of HIV.

“Alpha-defensins are promising as a future addition to the HIV treatment arsenal” said Dr David Ho, Director of ADARC and one of the study authors, adding that researchers at his centre were already “pursuing new therapeutic approaches based on the data published today.”

Investigators have established that a purified form of alpha-defensins are between 10 and 20 times more potent than synthetic forms of the protein and are now working on ways of further improving the protein’s potency using genomic and proteomic techniques.

In their research, investigators at ADARC compared the CD8 cells of long-term non-progressors and those from people with HIV whose immune systems were starting to fail. Alpha-defensin-1,-2 and -3 were found in all the people who remained healthy but in none of the people whose HIV infection had progressed.

However, when alpha-defensins were stripped from the CD8 cells of long-term non-progressors, investigators found that their HIV-inhibiting properties were eliminated.

“By understanding how some people’s immune systems are able to control HIV infection we may be able to develop new treatments to take advantage of this phenomenon” said Dr Linqi Zhang of ADARC, one of the study authors.