Human cytomegalovirus (CMV) hides inside white blood cells, and in most people it usually remains dormant and undetected for decades. If it is reactivated in a healthy individual, it usually does not cause symptoms. However, when it comes to immunosuppressed people, for example due to being on immunosuppressive treatment after undergoing an organ transplant, CMV infection can cause serious complications.
Now, a group of researchers from the University of Vrije-Amsterdam in the Netherlands and the University of Cambridge in the UK have developed a nanobody – a small fragment of a llama antibody – that can ward off CMV while it hides. of the immune system, allowing immune cells to detect and eliminate this potentially deadly pathogen that is one of the main causes of rejection of a transplanted organ.
“This approach reactivates the virus enough to make it visible to the immune system, but not enough to do what a virus normally does: replicate and spread.”
Ian Groves, from the Department of Medicine, University of Cambridge, said: “Our team has shown that llama-derived nanobodies have the potential to outwit human cytomegalovirus. This could be very important, as the virus can cause life-threatening complications in people whose immune systems are not working properly.”
A treatment to prevent or reduce CMV infection
Nanobodies were first identified in camels and exist in all camelids, including llamas. “As their name suggests, nanobodies are much smaller than normal antibodies, making them well suited to particular types of antigens and relatively easy to make and configure. For this reason, they are considered to have the potential to revolutionize antibody therapies”, explained Timo De Groof, from the University of Amsterdam and joint first author of the study. In fact, they had already been studied to combat Huntington’s disease, or the coronavirus.
In the new research, which has been published in Nature Communications, scientists have developed nanobodies that target a specific virus protein (US28), which can be detected on the surface of a latently infected CMV cell. They carried out experiments in the laboratory with cytomegalovirus-infected blood and showed that the nanobody binds to the US28 protein and suspends the signals that are established through the protein and help keep the virus in its latent state.
“Nanobodies are much smaller than normal antibodies, which makes them well suited to particular types of antigens and relatively easy to fabricate and configure.”
This allows immune cells to detect that the cell is infected and to trap and destroy the virus. The first author of the work, Elizabeth Elder, has declared that “the beauty of this approach is that it reactivates the virus enough to make it visible to the immune system, but not enough to do what a virus normally does: replicate and spread. The virus is forced to peek over the parapet where it can then be destroyed by the immune system.”
Professor Martine Smit of the University of Vrije-Amsterdam concluded that they believe their approach “could lead to a new type of treatment to reduce – and potentially even prevent – CMV infections in patients eligible for organ transplants. or stem cells.
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