Scientists launch a pre-emptive strike on deadly post-transplant infection


24-02-2021
  Surgeons at work in an operating theatre  Credit: Sasin Tipchai via Pixabay

A potential new treatment to protect immunosuppressed patients from human cytomegalovirus (HCMV) has been discovered by scientists at the University of Cambridge.

Their study shows that certain epigenetic inhibitors expose and help to destroy dormant HCMV infections, which often reactivate to cause serious illness and death in these vulnerable groups. Subject to clinical trials, their proposed ‘shock and kill’ treatment strategy offers hope to transplant patients across the world.

Around 80% of the UK population is currently infected with human cytomegalovirus (HCMV) and in developing countries this can be as high as 95%. The virus can remain dormant in our white blood cells for decades and, if it reactivates in a healthy individual, does not usually cause symptoms. But, for people who are immunocompromised, HCMV reactivation can be devastating. 

HCMV reactivation has been identified in COVID-19 patients, though scientists do not yet understand the relationship between the two viruses. Reactivation or re-infection in transplant recipients can lead to severe illness, including organ rejection and, in some cases, death.

More than 200,000 kidney, lung and stem cell transplants take place globally every year and HCMV reactivation occurs in more than half of these cases. For reasons scientists don’t yet fully understand, immunosuppressants appear to encourage the virus to reactivate as well as compromising the patient’s ability to fight it. There remains no effective vaccine against HCMV and anti-viral therapies often prove ineffective or detrimental.

Now, a team from the University of Cambridge’s School of Clinical Medicine has identified a drug type and treatment strategy that could dramatically reduce these devastating reactivation events. The study, published in the journal PNAS, describes how scientists exposed HCMV-infected blood samples to a wide-range of ‘epigenetic inhibitors’ – drugs widely used in cancer treatment – hoping to prompt the latent virus to produce proteins or targetable antigen that are visible to our immune system. 

They discovered that a particular group of these drugs, ‘bromodomain inhibitors’, successfully reactivated the virus by forcing it to convert its hidden genetic instructions into protein. This then enabled T-cells in the blood samples to target and kill these previously undetectable infected cells. 

The study is the first to identify the involvement of human host bromodomain (BRD) proteins in the regulation of HCMV latency and reactivation but also proposes a novel ‘shock and kill’ treatment strategy to protect transplant patients.

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Image:  Surgeons at work in an operating theatre

Credit: Sasin Tipchai via Pixabay

Reproduced courtesy of the University of Cambridge

 

 

The University of Cambridge is acknowledged as one of the world's leading higher education and research institutions. The University was instrumental in the formation of the Cambridge Network and its Vice- Chancellor, Professor Stephen Toope, is also the President of the Cambridge Network.

University of Cambridge (cam.ac.uk)