Tag Archives: Wellcome Trust

Discovery of HIV ‘invisibility cloak’ reveals new treatment opportunities

HIVGLASS

“Glass Microbiology” by Luke Jerram. (See: https://blog.lass.org.uk/2013/01/23/2393/) for artwork details. (Image unrelated to story).

Scientists have discovered a molecular invisibility cloak that enables HIV, the virus that causes AIDS, to hide inside cells of the body without triggering the body’s natural defence systems.

Their study shows how ‘uncloaking’ the virus using an experimental drug triggers an immune response that stops the virus from replicating in cells grown in the laboratory. The findings could lead to new treatments and help to improve existing therapies for HIV infection.

The innate immune system is the body’s first line of defence against infection and incorporates an alarm system present in all cells of the body that detects the presence of ‘foreign’ material from invading bacteria and viruses. When the alarm is tripped, the infected cell begins an antiviral programme and sends out warning signals to alert other cells that a virus is around.

HIV infects vital cells of the immune system, so its ability to replicate undetected without triggering this alarm system has puzzled scientists since the discovery of the virus.

The team identified two molecules inside host cells that are recruited by HIV after infection that stop the virus from reproducing its genetic material too early. The effect is to shield the virus from the alarm system and stop the innate immune system from kicking into action.

In the absence of these molecules, whether caused by depletion from infected cells or by blocking their recruitment using an experimental drug, HIV is exposed to the alarm system and an antivirus immune response is triggered. Targeting the cloaking molecules and not the virus itself makes it much more difficult for the virus to mutate and become resistant to this treatment approach, a significant problem with standard HIV therapies.

Professor Greg Towers, a Wellcome Trust Senior Research Fellow at UCL and lead author of the study, said: “HIV is extremely adept at hiding from our body’s natural defences, which is part of the reason the virus is so dangerous. Now we’ve identified the virus’ invisibility cloak, and how to expose it, we’ve uncovered a weakness that could be exploited for new HIV treatments.

“There’s a great deal more research needed, but the potential for this approach is huge – as a possible treatment in itself, but also as a complement to existing therapies. We’re also interested to see whether blocking these cloaking molecules can help to boost immune responses to experimental vaccines against HIV or be used to protect against HIV transmission.

“The hope is that one day we may be able develop a treatment that helps the body to clear the virus before the infection is able to take hold.”

The experimental drug used in the study is based on cyclosporine, a drug that is widely used to prevent organ rejection in transplant patients because of its ability to dampen the immune response. Cyclosporines have been shown to block the replication of HIV and other viruses but are not suitable for treating infected patients because of their negative effects on the immune system.

The team used a modified version of the drug, which blocks the effects of the two cloaking molecules without suppressing immune activity.

Dr Kevin Moses, Director of Science Funding at the Wellcome Trust, said: “In 2012, 2.3 million people were newly infected with HIV. While existing treatments are helping people with HIV to live longer and healthier lives, the challenge of adherence to treatment programmes means that drug resistance remains a threat and the virus continues to burden the world’s poorest communities. Understanding how HIV interacts with the body’s own defences might just be crucial for developing the best approaches to therapy.”

The study is published today in the journal ‘Nature’ and was funded by the Wellcome Trust, the Medical Research Council and the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

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HIV research offers hope

Issue 89 - Scaling up treatment guidelines in resource limited settings

Immediate treatment of HIV can slow the progression of the virus, a study undertaken by researchers from the University of Oxford, Imperial College London and the Medical Research Council’s Clinical Trials Unit has shown.

Antiretroviral medication taken during the early stages of infection, over a 48-week period, delays damage to the immune system and can defer the need for long-term treatment.

An estimated 34 million people suffer from HIV worldwide. The virus weakens the immune system, leaving the body vulnerable to infection. In its early stages it often goes unnoticed; left unchecked, it can result in individuals being in danger of life-threatening illnesses.

The study, which took place over five years, took the form of a randomised controlled trial of antiretroviral treatment on 366 adults from Australia, Brazil, Ireland, Italy, South Africa, Spain, Uganda and the UK. It comprised mostly of heterosexual women and gay men and was funded by the Wellcome Trust.

At present, it is unusual for antiretroviral medication to be given to HIV patients in the early stages of infection. The trial randomly allocated the volunteers, who had been diagnosed with HIV no more than six months earlier, medication for 48 weeks, 12 weeks or not at all.

On average, the study found that those receiving no medication required a lifelong course of treatment 157 weeks after infection. Those receiving 12 weeks of antiretroviral medication took an average of 184 weeks before receiving lifelong treatment. Participants on the 48 week course began long-term treatment on average 222 weeks after infection.

Moreover, those receiving medication for 48 weeks had higher CD4 T-cell counts, which can reduce susceptibility to secondary infections such as tuberculosis. Adults on this course recorded lower levels of HIV in the blood, which could help reduce the risk of infection for sexual partners.

Dr Sarah Fidler, leader of the study from Imperial College London said: “These results are very promising and suggest that a year-long course of treatment for people recently infected with HIV may have some benefit on both the immune system as well as helping control the virus.”

Concerns over how cost-effective such treatment would be have been raised by some who do not deem the findings to be tremendously significant. Professor Gita Ramjee, who led the study in South Africa, commented: “We now need to weigh up whether the benefits offered by early intervention are outweighed by the strategic and financial challenges such a change in policy would incur, particularly in resource-poor settings such as Africa, although this may be where the most benefits are seen in terms of TB rates.”

Students at Oxford University have expressed interest in this new study. Fergus Chadwick, a Biologist, said: “It is really fascinating to see how theory that has been outlined in our lectures is being applied in the real world with such promising results.”

Original Article by Elizabeth Pugh at Oxfordstudent.com

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