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Hormones could explain why women progress faster to AIDS

Agence France-Presse - July 13, 2009


PARIS, July 13, 2009 (AFP) - Scientists in the United States said on Monday they could help explain why women infected with the human immunodeficiency virus (HIV) advance faster to AIDS than men.

One of the enigmas about the AIDS pandemic is why women, after infection with HIV-1, seem better able to combat the virus in its early stages but then advance faster to AIDS compared to men infected with a similar level of the virus.

The answer lies in the response of a key component in their immune system, and hormonal differences may account for it, according to a paper published online by the journal Nature Medicine.

If right, it throws up new possibilities for drugs that would hinder the process, its authors added.

The study focuses on plasmacytoid dendritic cells (pDCs), which are "first responders" in the immune system. They detect a microbial intruder and then alert other defenders.

The pDCs recognise the AIDS virus through a little docking point called Toll-like receptor 7, or TLR7. Once their TLR7 is switched on, the pDCs call up an important immune-system molecule called interferon alpha.

Researchers at the Ragon Institute of the Massachusetts General Hospital were intrigued by lab-dish tests that showed higher levels of the female hormone progesterone intensified pDC activation.

The team then linked interferon alpha to the activation of one of the heavy artillery of the immune system -- CD8 cells.

Previous research has already spotted an intriguing phenomenon.

The more CD8 cells that are stimulated, the faster a patient progresses to acquired immune deficiency syndrome (AIDS), the stage whereby the immune system is so devastated that the body becomes prey to opportunistic disease. Why this is so is unclear, though.

Ragon Institute investigator Marcus Altfeld said that the results suggest men and women may differ in an important way in how their immune systems respond to HIV.

In the early stages of infection, a stronger activation of their immune system could be beneficial to women, he said.

But in the long run, the persistent viral replication and chronic activation of the immune system -- as indicated by the CD8 cells -- can lead to faster progression to AIDS.

Altfeld said the study raised new questions about how sex hormones modulate the molecular cascade to HIV infection. One interesting idea, he added, could be a drug that stops or slows the TLR7 alarm system.

"Focussing on immune activation separately from viral replication might give us new therapeutic approaches" to tackling the virus, he said in a press release.

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