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.
Image: A glass sculpture of HIV. Credit: Luke Jerram.
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Notes to editors
Rasaiyaah J et al. HIV-1 evades innate immune recognition through specific co-factor recruitment. Nature 2013 (epub ahead of print).
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Over the past century, the Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed.
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The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world.