07 February 2007

Molecule helps fight HIV

US Aids researchers are getting a better understanding of how an immune system molecule called interleukin-7 keeps cells from dying, even when they're under attack from HIV.

US Aids researchers are getting a better understanding of how an immune system molecule called interleukin-7 keeps cells from dying, even when they're under attack from HIV.

Clinical trials are already under way in which scientists are boosting HIV-positive patients' IL-7 levels to improve their immune health.

"We desperately need some way of protecting cells from dying in Aids," said Rowena Johnston, vice president of research at the Foundation for Aids Research (amfAR) in New York City.

No replacement for HAART
While IL-7 therapy would never replace current highly active antiretroviral therapy (HAART) for patients, it might help repair the lasting damage that HIV inflicts on the immune system, she said.

"Because, even in the first few weeks of infection - before you even know that you have HIV and haven't started therapy yet - there is this lasting damage to the immune system that HIV does," Johnston noted. "That is something that absolutely needs to be addressed."

Johnston was not involved in the study, which was conducted by a team at the US National Institute of Allergy and Infectious Diseases (NIAID). The researchers published their findings in this week's Proceedings of the National Academy of Sciences.

IL-7 is one of a number of interleukin molecules that the body uses as "long-range messengers" to recruit an immune response to sites of injury in the body, explained lead researcher Paolo Lusso. He is an adjunct investigator in the Laboratory of Immunoregulation at NIAID.

Keeps T-cells alive
According to Lusso, IL-7, especially, is "recognised to be key to the well-being of the T-cell." T-cells are a type of immune system killer cell, as well as a regulatory cell.

A major subset of T-cells, called CD4-positive T-cells, are also the prime target of HIV. As the virus enters and kills these cells, it slowly destroys the human immune system, leaving Aids patients vulnerable to deadly infections.

But "IL-7 helps keep T-cells alive," Lusso said. "When you get any knocks or damage that lowers the number of [T-cell] lymphocytes, IL-7 turns on to try and rebalance the situation."

With that in mind, researchers have long investigated the IL-7 molecule as a possible therapy. In fact, a clinical trial using IL-7 as adjunct therapy in HIV-positive patients is set to announce its findings in March, Lusso said.

The NIAID trial looked at the issue from a different angle, trying to discover just how IL-7 protects T-cells from harm.

How the study was conducted
In their laboratory experiments, Lusso and his co-researchers took blood samples from 24 HIV-infected patients at varying stages of infection. They then added an extra dose of IL-7 to the samples and observed T-cell survival.

"What we found is that IL-7 prevents the apoptosis of CD4 cells in HIV-infected patients," he said.

Apoptosis - programmed cell death - is a natural phenomenon common to nearly all cells. One of the ways that HIV kills T-cells is by driving them into apoptosis way too early, scientists say.

The new study experiments also showed that IL-7 delayed HIV-related apoptosis in another form of T-cell, the CD8-positive T-cell, Lusso said.

Little effect on healthy cells
And the study turned up another welcome surprise. "If you administer IL-7 to normal cells in an uninfected individual, the effect is close to zero," Lusso said. "That's good, because you want to maintain those healthy, physiological levels of apoptosis."

In fact, IL-7 therapy was most protective in samples from sicker patients with the lowest CD4 T-cell counts - exactly those populations doctors would most like to help.

While the findings are heartening, Lusso said "there's no way that [IL-7 therapy] would substitute for HAART. But it may be beneficial."

The therapy might prove especially useful in limiting the long-lasting immune system damage that occurs within the first few days of infection. According to Lusso, that damage is like a "scar" that lingers on the immune response, dampening its function even after HIV levels have been suppressed.

To be tested in monkeys
"We are actually planning an experiment in monkeys that will start in the next few weeks," Lusso said. "We'd like to give them IL-7 early, before HIV gets into the body in a really pervasive way, to see if we can prevent the formation of that [immune system] scar."

"Then, maybe you could go with HAART full steam ahead, suppress the virus and prevent the damage that the virus does even within that short space of time," he explained.

But Lusso stressed that patients shouldn't pin too much hope on IL-7, which is also under development as potential cancer therapy. While it's thought to be relatively safe, the treatment might have unforeseen side-effects down the line, he said.

"The [immune] system is so complicated and interrelated - you can do something good on one side and cause something bad on the other side," he said. "We have to watch what happens here."

A fine balance
Johnston, of amfAR, agreed. "It's all such a fine balance," she said. "Any change in any one of those ingredients can have vast repercussions for how the whole system works."

In a related study, also published in this week's Proceedings of the National Academy of Sciences, scientists at the US National Cancer Institute said they have discovered how a virus responsible for some T-cell leukemias evades the body's immune defences.

The virus, called human T-cell leukaemia virus type 1 (HTLV-1), can block the packaging of an immune system enzyme called hA3G within viral particles. Under normal circumstances, the body uses hA3G to stop the virus from replicating, but HTLV-1 seems to inhibit this activity, researchers said.

However, in their experiments, the researchers were able to tweak certain amino acids within HTLV-1 and boost the protective activity of hA3G. The finding could "possibly assist in preventing some types of cancer," NCI director Dr John E. Niederhuber said in a statement. – (HealthDayNews)

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HIV/Aids Centre

February 2007


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Dr Sindisiwe van Zyl qualified at the University of Pretoria before working for an HIV/AIDS NPO in Soweto for many years. She was named one of the Mail & Guardian's Top 200 Young South Africans in 2012.

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