Scientists Discover Natural Barrier to HIV

News  HealthDay. Monday, 5 March 2007.

E.J. Mundell

Foreskin cells provide Natural Barrier to HIV

MONDAY, March 5 (HealthDay News) – Researchers have discovered that cells in the mucosal lining of human genitalia produce a protein that eats up invading HIV -- possibly keeping the spread of the AIDS more contained than it might otherwise be.

Even more important, enhancing the activity of this protein, called Langerin, could be a potent new way to curtail the transmission of the virus that causes AIDS, the Dutch scientists added.

Langerin is produced by Langerhans cells, which form a web-like network in skin and mucosa. This network is one of the first structures HIV confronts as it attempts to infect its host.

However, we observed that Langerin is able to scavenge viruses from the surrounding environment, thereby preventing infection, said lead researcher Teunis Geijtenbeek, an immunologist researcher at External link Vrije University Medical Center in Amsterdam.

And since generally all tissues on the outside of our bodies have Langerhans cells, we think that the human body is equipped with an antiviral defense mechanism, destroying incoming viruses, Geijtenbeek said.

The finding, reported in the March 4 online issue of Nature Medicine, is very interesting and unexpected, said Dr. Jeffrey Laurence, director of the Laboratory for AIDS Virus Research at the External link Weill Cornell Medical College, in New York City. It may explain part of the relative inefficiency of HIV in being transmitted.

Even though HIV has killed an estimated 22 million people since it was first recognized more than 25 years ago, it is actually not very good at infecting humans, relatively speaking.

For example, the human papillomavirus (HPV), which causes cervical cancer, is nearly 100 percent infectious, Laurence noted. That means that every encounter with the sexually transmitted virus will end in infection.

On the other hand, during one episode of penile-vaginal intercourse with an HIV-infected partner, the chance that you are going to get HIV is somewhere between one in 100 and one in 200, Laurence said.

Experts have long puzzled why HIV is relatively tough to contract, compared to other pathogens. The Dutch study, conducted in the laboratory using Langerhans cells from 13 human donors, may explain why.

When HIV comes in contact with genital mucosa, its ultimate target – the cells it seeks to hijack and destroy – are immune system T-cells. But T-cells are relatively far away (in lymph tissues), so HIV uses nearby Langerhans cells as vehicles to migrate to T-cells.

For decades, the common wisdom was that HIV easily enters and infects Langerhans cells. Geijtenbeek's team has now cast doubt on that notion.

Looking closely at the interaction of HIV and Langerhans cells, they found that the cells do not become infected by HIV-1, because the cells have the protein Langerin on their cell surface, Geijtenbeek said. Langerin captures HIV-1 very efficiently, and this Langerin-bound HIV-1 is taken up (a bit like eating) by the Langerhans cells and destroyed.

In essence, Geijtenbeek said, Langerhans cells act more like a virus vacuum cleaner.

Only in certain circumstances – such as when levels of invading HIV are very high, or if Langerin activity is particularly weak – are Langerhans cells overwhelmed by the virus and infected.

The finding is exciting for many reasons, not the least of which is its potential for HIV prevention, Geijtenbeek said.

We are currently investigating whether we can enhance Langerin function by increasing the amount of Langerin on the cell surface of Langerhans cells, he said. This might be a real possibility, but it will take time. I am also confident that other researchers will now also start exploring this possibility.

The discovery might also help explain differences in vulnerability to HIV infection among people.

It is known that the Langerin gene is different in some individuals, Geijtenbeek noted. These differences could affect the function of Langerin. Thus, Langerhans cells with a less functional Langerin might be more susceptible to HIV-1, and these individuals are more prone to infection. We are currently investigating this.

The finding should also impact the race to find topical microbicides that might protect women against HIV infection. Choosing compounds that allow Langerin to continue to work its magic will enhance any candidate microbicide's effectiveness, the Dutch researcher said.

Laurence did offer one note of caution, however.

In the test tube, this is a very important finding, he said. But there are many things in the test tube that don't occur when you get into an animal or a human. Having said that, though, this is a very intriguing finding.


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